THERAPEUTIC COMPOUNDS AND METHODS OF USE CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to and benefit of U.S. Provisional Patent Application No. 62/935,015, filed November 13, 2019, and U.S. Provisional Patent Application No. 63/056,502, filed July 24, 2020, the disclosures of each of which are hereby incorporated herein by reference in their entirety. SEQUENCE LISTING [0001.1] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on November 11, 2020, is named P35805-WO_SL.txt and is 34,037 bytes in size. FIELD OF THE DISCLOSURE [0002] The present disclosure relates to compounds useful for therapy and/or prophylaxis in a mammal, and in particular as inhibitors of TEAD useful for treating cancer. BRIEF DESCRIPTION [0003] The Hippo pathway is a signaling pathway that regulates cell proliferation and cell death and determines organ size. The pathway is believed to play a role as a tumor suppressor in mammals, and disorders of the pathway are often detected in human cancers. The pathway is involved in and/or may regulate the self-renewal and differentiation of stem cells and progenitor cells. In addition, the Hippo pathway may be involved in wound healing and tissue regeneration. Furthermore, it is believed that as the Hippo pathway cross-talks with other signaling pathways such as Wnt, Notch, Hedgehog, and MAPK/ERK, it may influence a wide variety of biological events, and that its dysfunction could be involved in many human diseases in addition to cancer. For reviews, see, for example, Halder et al., 2011, Development 138:9-22; Zhao et al., 2011, Nature Cell Biology 13:877-883; Bao et al., 2011, J. Biochem.149:361-379; Zhao at al., 2010, J. Cell Sci.123:4001-4006. [0004] The Hippo signaling pathway is conserved from drosophila to mammals (Vassilev et al., Genes and Development, 2001, 15, 1229-1241; Zeng and Hong, Cancer Cell, 2008, 13, 188- 192). The core of the pathway consists of a cascade of kinases (Hippo-MST1-2 being upstream of Lats 1-2 and NDRI-2) leading to the phosphorylation of two transcriptional co-activators, YAP (Yes-Associated Protein) and TAZ (Transcription co-activator with PDZ binding motif or tafazzin; Zhao et al., Cancer Res., 2009, 69, 1089-1098; Lei et al., Mol. Cell. Biol., 2008, 28, 2426-2436). [0005] Because the Hippo signaling pathway is a regulator of animal development, organ size control and stem cell regulation, it has been implicated in cancer development (Review in Harvey et al., Nat. Rev. Cancer, 2013, 13, 246-257; Zhao et al., Genes Dev.2010, 24, 862-874). In vitro, the overexpression of YAP or TAZ in mammary epithelial cells induces cell transformation, through interaction of both proteins with the TEAD family of transcription factors. Increased YAP/TAZ transcriptional activity induces oncogenic properties such as epithelial- mesenchymal transition and was also shown to confer stem cells properties to breast cancer cells. In vivo, in mouse liver, the overexpression of YAP or the genetic knockout of its upstream regulators MST1-2 triggers the development of hepatocellular carcinomas. Furthermore, when the tumor suppressor NF2 is inactivated in the mouse liver, the development of hepatocellular carcinomas can be blocked completely by the co-inactivation of YAP. [0006] It is believed that deregulation of the Hippo tumor suppressor pathway is a major event in the development of a wide range of malignancies, including with no limitations, lung cancer (NSCLC; Zhou et al., Oncogene, 2011, 30, 2181-2186; Wang et al., Cancer Sci., 2010, 101, 1279-1285), breast cancer (Chan et al., Cancer Res., 2008, 68, 2592-2598; Lamar et al., Proc. Natl. Acad. Sci, USA, 2012; 109, E2441-E2250; Wang et al., Eur. J. Cancer, 2012, 48, 1227-1234), head and neck cancer (Gasparotto et al., Oncotarget., 2011, 2, 1165-1175; Steinmann et al., Oncol. Rep., 2009, 22, 1519-1526), colon cancer (Angela et al., Hum. Pathol., 2008, 39, 1582-1589; Yuen et al., PLoS One, 2013, 8, e54211; Avruch et al., Cell Cycle, 2012, 11, 1090-1096), ovarian cancer (Angela et al., Hum. Pathol., 2008, 39, 1582-1589; Chad et al., Cancer Res., 2010, 70, 8517-8525; Hall et al., Cancer Res., 2010, 70, 8517-8525), liver cancer (Jie et al., Gastroenterol. Res. Pract., 2013, 2013, 187070; Ahn et al., Mol. Cancer. Res., 2013, 11, 748-758; Liu et al., Expert. Opin. Ther. Targets, 2012, 16, 243-247), brain cancer (Orr et al., J Neuropathol. Exp. Neurol.2011, 70, 568-577; Baia et al., Mol. Cancer Res., 2012, 10, 904-913; Striedinger et al., Neoplasia, 2008, 10, 1204-1212) and prostate cancer (Zhao et al., Genes Dev., 2012, 26, 54-68; Zhao et al., Genes Dev., 2007, 21, 2747-2761), mesotheliomas (Fujii et al., J. Exp. Med., 2012, 209, 479-494; Mizuno et al., Oncogene, 2012, 31, 5117-5122; Sekido Y., Pathol. Int., 2011, 61, 331-344), sarcomas (Seidel et al., Mol. Carcinog., 2007, 46, 865-871) and leukemia (Jimenez-Velasco et al., Leukemia, 2005, 19, 2347-2350). [0007] Two of the core components of the mammalian Hippo pathway are Lats1 and Lats2, which are nuclear Dbf2-related (NDR) family protein kinases homologous to Drosophila Warts (Wts). The Lats1/2 proteins are activated by association with the scaffold proteins Mob1A/B (Mps one binder kinase activator-like 1A and 1B), which are homologous to Drosophila Mats. Lats1/2 proteins are also activated by phosphorylation by the STE20 family protein kinases Mst1 and Mst2, which are homologous to Drosophila Hippo. Lats1/2 kinases phosphorylate the downstream effectors YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif; WWTR1), which are homologous to Drosophila Yorkie. The phosphorylation of YAP and TAZ by Lats1/2 are crucial events within the Hippo signaling pathway. Lats1/2 phosphorylates YAP at multiple sites, but phosphorylation of Ser127 is critical for YAP inhibition. Phosphorylation of YAP generates a protein-binding motif for the 14-3-3 family of proteins, which upon binding of a 14-3-3 protein, leads to retention and/or sequestration of YAP in the cell cytoplasm. Likewise, Lats1/2 phosphorylates TAZ at multiple sites, but phosphorylation of Ser89 is critical for TAZ inhibition. Phosphorylation of TAZ leads to retention and/or sequestration of TAZ in the cell cytoplasm. In addition, phosphorylation of YAP and TAZ is believed to destabilize these proteins by activating phosphorylation-dependent degradation catalyzed by YAP or TAZ ubiquitination. Thus, when the Hippo pathway is “on”, YAP and/or TAZ is phosphorylated, inactive, and generally sequestered in the cytoplasm; in contrast, when the Hippo pathway is “off”, YAP and/or TAZ is non-phosphorylated, active, and generally found in the nucleus. [0008] Non-phosphorylated, activated YAP is translocated into the cell nucleus where its major target transcription factors are the four proteins of the TEAD-domain-containing family (TEAD1-TEAD4, collectively “TEAD”). YAP together with TEAD (or other transcription factors such as Smad1, RUNX, ErbB4 and p73) has been shown to induce the expression of a variety of genes, including connective tissue growth factor (CTGF), Gli2, Birc5, Birc2, fibroblast growth factor 1 (FGF1), and amphiregulin (AREG). Like YAP, non-phosphorylated TAZ is translocated into the cell nucleus where it interacts with multiple DNA-binding transcription factors, such as peroxisome proliferator-activated receptor γ (PPARγ), thyroid transcription factor-1 (TTF-1), Pax3, TBX5, RUNX, TEAD1 and Smad2/3/4. Many of the genes activated by YAP/TAZ- transcription factor complexes mediate cell survival and proliferation. Therefore, under some conditions YAP and/or TAZ acts as an oncogene and the Hippo pathway acts as a tumor suppressor. [0009] Hence, pharmacological targeting of the Hippo cascade through inhibition of TEAD would be valuable approach for the treatment of cancers that harbor functional alterations of this pathway. SUMMARY OF THE DISCLOSURE [0010] In some aspects, a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, of the following formula (B-1) is provided: or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: X1 is N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C _1-6 alkyl of R ₅ is optionally substituted with hydroxyl or N(R ^e )(R ^f ), or the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl; X2 is N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH ₂ , N(R ^e )(R ^f ), C _3-10 cycloalkyl, C _1-6 alkoxy, C _6-20 aryl, and C _1-6 alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ); X ₃ is N or C-H, provided that, when X ₃ is N, and R ₁ is then at least one of X ₁ and X2 is N; R ₁ is: (i) oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with one or more -C(O)NH ₂ , and L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) N(R ^e )(CN), and L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or _(iii) , wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH ₂ -O-**, *-O-CH ₂ -**, - CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iv) , wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C1- ₆ alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; R2 is C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- ₁₃ spirocyclyl, or 5-20 membered heteroaryl, wherein the C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, C _5- 13spirocyclyl, or 5-20 membered heteroaryl of R2 is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- ₆ haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), O(R ^e ), and SF ₅ , provided that, when R2 is C1-12alkyl, wherein the C1-12alkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1- ₆ alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), then L is -CH=CH- or -C≡C-; R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), or R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH, or R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, provided that: (i) when R ₃ is cyano, C _1-6 alkyl, C _1-4 alkoxy, or C _2-4 alkenyl, wherein the C _2-4 alkenyl is optionally substituted with N(R ^e )(R ^f ), and R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, and (ii) when R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, and X ₃ is CH, and R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is absent or is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, and (iii) when R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl, and then R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ); R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl; and R ^e and R ^f are, independently of each other and independently at each occurrence, selected from the group consisting of H, cyano, hydroxyl, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl of R ^e and R ^f are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. [0011] In some aspects, a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, of the following formula (B) is provided: or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: X ₁ is N or C-R ₅ , wherein each R ₅ is independently selected from the group consisting of H, cyano, halo, C(O)NH ₂ , N(R ^e )(R ^f ), C _3-10 cycloalkyl, C _1-6 alkoxy, C _6-20 aryl, and C _1-6 alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ), or the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl, provided that X ₃ is CH; X ₂ is N or C-R ₅ , wherein each R ₅ is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ); X3 is N or C-H, provided that, when X3 is N, and R1 is then at least one of X1 and X 2 is N; R1 is: (i) oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C1-6alkyl, and L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) N(R ^e )(CN), and L is absent or is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or _(iii) , wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH ₂ -O-**, *-O-CH ₂ -**, - CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iv) , wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C _1- 6alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; R ₂ is C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, C _5- 13spirocyclyl, or 5-20 membered heteroaryl, wherein the C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- ₁₃ spirocyclyl, or 5-20 membered heteroaryl of R ₂ is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1- 6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), provided that, when R2 is C1-12alkyl, wherein the C1-12alkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is -CH=CH- or -C≡C-; R ₃ is cyano, C _1-6 alkyl, C _1-4 alkoxy, or C _2-4 alkenyl, wherein the C _2-4 alkenyl is optionally substituted with N(R ^e )(R ^f ), or R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH, or R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, provided that: (i) when R ₃ is cyano, C _1-6 alkyl, C _1-4 alkoxy, or C _2-4 alkenyl, wherein the C _2-4 alkenyl is optionally substituted with N(R ^e )(R ^f ), and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) when R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH, and R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _{1- 6} alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), then L is absent or is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iii) when R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl, and then R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ); R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl; and R ^e and R ^f are, independently of each other and independently at each occurrence, selected from the group consisting of H, cyano, hydroxyl, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl of R ^e and R ^f are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. [0012] In some aspects of the present disclosure, the compounds, or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, are of the following formula (I): wherein: X1 and X2 are each independently N or C-R5, wherein R5 is selected from the group consisting of hydrogen, cyano, halo, C(O)NH2, NH(R ^e ), C1-6alkyl, C3-10cycloalkyl, C1-6alkoxy, and C6-20aryl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl; X3 is N or CH, provided that, when X3 is N, at least one of X1 and X2 is N; R ₁ is , wherein R _a , R _b , and R _c are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or R1 is , wherein wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; R ₂ is C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, or C _5- 13spirocyclyl, wherein the C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6- 20aryl, or C5-13spirocyclyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3- 10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3- 10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl, provided that, when R2 is C1-12alkyl, wherein the C1-12alkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), L is -CH=CH- or -C≡C-; R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with NH(R ^e ); or R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, provided that X ₃ is CH; or R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, provided that: (i) when R ₃ is cyano, C _1-6 alkyl, C _1-4 alkoxy, or C _2-4 alkenyl, wherein the C _2-4 alkenyl is optionally substituted with N(R ^e )(R ^f ), and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (ii) when R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, provided that X ₃ is CH, and R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is absent or is *-CH2-O-**, -CH=CH-, or - C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iii) when R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; and R ₄ is H or C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl. [0013] In some aspects, a pharmaceutical composition comprising a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient, is provided. [0014] In some aspects, a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for use in medical therapy. [0015] In some aspects, a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the treatment or prophylaxis of cancer, mesothelioma, sarcoma, or leukemia. [0016] In some aspects, a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the preparation of a medicament for the treatment or prophylaxis of cancer, mesothelioma, sarcoma, or leukemia. [0017] In some aspects, a method for treating cancer, mesothelioma, sarcoma, or leukemia in a mammal is provided, the method comprising, administering a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal. [0018] In some aspects, a method for treating cancer, mesothelioma, sarcoma, or leukemia in a mammal is provided, the method comprising, administering a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal in combination with a second therapeutic agent. [0019] In some aspects, a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for modulating TEAD activity. [0020] In some aspects, a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for the treatment or prophylaxis of a disease or condition mediated by TEAD activity. [0021] In some aspects, a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is provided for use for the preparation of a medicament for the treatment or prophylaxis of a disease or condition that is mediated by TEAD activity. [0022] In some aspects, a method for modulating TEAD activity is provided, the method comprising contacting TEAD with a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0023] In some aspects, a method for treating a disease or condition mediated by TEAD activity in a mammal is provided, the method comprising administering a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal. DETAILED DESCRIPTION DEFINITIONS [0024] Unless otherwise indicated, the following specific terms and phrases used in the description and claims are defined as follows. [0025] The term “moiety” refers to an atom or group of chemically bonded atoms that is attached to another atom or molecule by one or more chemical bonds thereby forming part of a molecule. [0026] The term “substituted” refers to the fact that at least one of the hydrogen atoms of that moiety is replaced by another substituent or moiety. [0027] The term “alkyl” refers to an aliphatic straight-chain or branched-chain saturated hydrocarbon moiety having 1 to 20 carbon atoms, such as 1 to 12 carbon atoms, or 1 to 6 carbon atoms. Alkyl groups may be optionally substituted. [0028] The term “cycloalkyl” means a saturated or partially unsaturated carbocyclic moiety having mono- or bicyclic (including bridged bicyclic) rings and 3 to 10 carbon atoms in the ring. In particular aspects, cycloalkyl may contain from 3 to 8 carbon atoms (i.e., (C3- C8)cycloalkyl). In other particular aspects cycloalkyl may contain from 3 to 6 carbon atoms (i.e., (C ₃ -C ₆ )cycloalkyl). Examples of cycloalkyl moieties include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and partially unsaturated (cycloalkenyl) derivatives thereof (e.g. cyclopentenyl, cyclohexenyl, and cycloheptenyl). The cycloalkyl moiety can be attached in a spirocycle fashion such as spirocyclopropyl: . [0029] The term “haloalkyl” refers to an alkyl group wherein one or more of the hydrogen atoms of the alkyl group has been replaced by the same or different halogen atoms, such as fluoro atoms. Examples of haloalkyl include monofluoro-, difluoro- or trifluoro-methyl, -ethyl or - propyl, for example 3,3,3-trifluoropropyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, fluoromethyl, or trifluoromethyl. Haloalkyl groups may be optionally substituted. [0030] The term “alkenyl” refers to a straight or branched chain alkyl or substituted alkyl group as defined elsewhere herein having at least one carbon-carbon double bond. Alkenyl groups may be optionally substituted. [0031] The term “alkynyl” refers to a straight or branched chain alkyl or substituted alkyl group as defined elsewhere herein having at least one carbon-carbon triple bond. Alkynyl groups may be optionally substituted. [0032] The terms “heterocyclyl” and “heterocycle” refer to a 4, 5, 6 and 7-membered monocyclic or 7, 8, 9 and 10-membered bicyclic (including bridged bicyclic) heterocyclic moiety that is saturated or partially unsaturated, and has one or more (e.g., 1, 2, 3 or 4) heteroatoms selected from oxygen, nitrogen and sulfur in the ring with the remaining ring atoms being carbon. When used in reference to a ring atom of a heterocycle, a nitrogen or sulfur may also be in an oxidized form, and a nitrogen may be substituted. The heterocycle can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocycles include, without limitation, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, pyrrolidonyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. Other examples of such saturated or partially unsaturated heterocycles include, without limitation, oxiranyl and oxetanyl. The term the term heterocycle also includes groups in which a heterocycle is fused to one or more aryl, heteroaryl, or cycloalkyl rings, such as indolinyl, 3H-indolyl, chromanyl, 2-azabicyclo[2.2.1]heptanyl, octahydroindolyl, or tetrahydroquinolinyl. Heterocyclyl groups may be optionally substituted. [0033] The term “aryl” refers to a cyclic aromatic hydrocarbon moiety having a mono-, bi- or tricyclic aromatic ring of 5 to 20 carbon ring atoms. Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, benzyl, and the like. The term “aryl” also includes partially hydrogenated derivatives of the cyclic aromatic hydrocarbon moiety provided that at least one ring of the cyclic aromatic hydrocarbon moiety is aromatic, each being optionally substituted. In some aspects, monocyclic aryl rings may have 5 or 6 carbon ring atoms. Aryl groups may be optionally substituted. [0034] The term “heteroaryl” refers an aromatic heterocyclic mono- or bicyclic ring system of 1 to 20 ring atoms, comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, the remaining ring atoms being carbon. Examples of heteroaryl moieties include pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, triazinyl, isoxazolyl, benzofuranyl, isothiazolyl, benzothienyl, indolyl, isoindolyl, isobenzofuranyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzooxadiazolyl, benzothiadiazolyl, benzotriazolyl, purinyl, quinolinyl, isoquinolinyl, quinazolinyl, or quinoxalinyl. Heteroaryl groups may be optionally substituted. [0035] The terms “halo” and “halogen” refer fluoro, chloro, bromo and iodo. In some aspects, halo is fluoro or chloro. [0036] The term “oxo” refers to the =O moiety. [0037] The term “cyano” refers to the -C≡N moiety. [0038] The terms “spirocycle” and “spirocyclyl” refer to carbogenic bicyclic ring systems comprising between 5 and 15 carbon atoms with both rings connected through a single atom. The rings can be different in size and nature, or identical in size and nature. Examples include spiropentane, spirohexane, spiroheptane, spirooctane, spirononane, or spirodecane. One or more of the carbon atoms in the spirocycle can be substituted with a heteroatom (e.g., O, N, S, or P), wherein in such aspects the spirocycle may comprise between 3 and 14 carbon atoms. Spirocycle groups may be optionally substituted. [0039] The term “annular” refers to a moiety that is a member of a ring, including, but not limited to, a cycloalkyl ring, a cycloalkenyl ring, an aryl ring, a heteroaryl ring, a heterocyclyl ring, or a spirocyclyl ring. For example, if a heteroaryl ring is described as “comprising two or more annular heteroatoms”, two or more of the ring members of the heteroaryl ring will be heteroatoms. [0040] The term “pharmaceutically acceptable salts” refers to those salts which retain the biological effectiveness and properties of the free bases or free acids, which are not biologically or otherwise undesirable. Salts may be formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, preferably hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, salicylic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p- toluenesulfonic acid, N-acetylcystein and the like. In addition, salts may be prepared by the addition of an inorganic base or an organic base to the free acid. Salts derived from an inorganic base include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, and magnesium salts and the like. Salts derived from organic bases include, but are not limited to salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N- ethylpiperidine, piperidine, polyamine resins and the like. [0041] The term “prodrug” refers to those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present disclosure. Additionally, prodrugs can be converted to the compounds of the present disclosure by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the present disclosure when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent. [0042] In some prodrug aspects, prodrugs include compounds wherein an amino acid residue, or a polypeptide chain of two or more (e.g., two, three or four) amino acid residues, is covalently joined through an amide or ester bond to a free amino, hydroxy or carboxylic acid group of a compound of the present disclosure. The amino acid residues include but are not limited to the 20 naturally occurring amino acids commonly designated by three letter symbols and also includes phosphoserine, phosphothreonine, phosphotyrosine, 4-hydroxyproline, hydroxylysine, demosine, isodemosine, gamma-carboxyglutamate, hippuric acid, octahydroindole-2-carboxylic acid, statine, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, penicillamine, ornithine, 3- methylhistidine, norvaline, beta-alanine, gamma-aminobutyric acid, citrulline, homocysteine, homoserine, methyl-alanine, para-benzoylphenylalanine, phenylglycine, propargylglycine, sarcosine, methionine sulfone and tert-butylglycine. [0043] In some other prodrug aspects, a free carboxyl group of a compound of the disclosure can be derivatized as an amide or alkyl ester. In yet other prodrug aspects, prodrugs comprising free hydroxy groups can be derivatized as prodrugs by converting the hydroxy group into a group such as, but not limited to, a phosphate ester, hemisuccinate, dimethylaminoacetate, or phosphoryloxymethyloxycarbonyl group, as outlined in Fleisher, D. et al., (1996) Improved oral drug delivery: solubility limitations overcome by the use of prodrugs Advanced Drug Delivery Reviews, 19:115. Carbamate prodrugs of hydroxy and amino groups are also included, as are carbonate prodrugs, sulfonate esters and sulfate esters of hydroxy groups. Derivatization of hydroxy groups as (acyloxy)methyl and (acyloxy)ethyl ethers, wherein the acyl group can be an alkyl ester optionally substituted with groups including, but not limited to, ether, amine and carboxylic acid functionalities, or where the acyl group is an amino acid ester as described above, are also encompassed. Prodrugs of this type are described in J. Med. Chem., (1996), 39:10. More specific examples include replacement of the hydrogen atom of the alcohol group with a group such as (C1-6)alkanoyloxymethyl, 1-((C1-6)alkanoyloxy)ethyl, 1-methyl-1-((C1- ₆ )alkanoyloxy)ethyl, (C _1-6 )alkoxycarbonyloxymethyl, N-(C _1-6 )alkoxycarbonylaminomethyl, succinoyl, (C1-6)alkanoyl, alpha-amino(C1-4)alkanoyl, arylacyl and alpha-aminoacyl, or alpha- aminoacyl-alpha-aminoacyl, where each alpha-aminoacyl group is independently selected from the naturally occurring L-amino acids, P(O)(OH) ₂ , -P(O)(O(C _1-6 )alkyl) ₂ or glycosyl (the radical resulting from the removal of a hydroxyl group of the hemiacetal form of a carbohydrate). [0044] For additional examples of prodrug derivatives, see, for example, a) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985) and Methods in Enzymology, Vol.42, p.309- 396, edited by K. Widder, et al. (Academic Press, 1985); b) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 “Design and Application of Prodrugs,” by H. Bundgaard p. 113-191 (1991); c) H. Bundgaard, Advanced Drug Delivery Reviews, 8:1-38 (1992); d) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77:285 (1988); and e) N. Kakeya, et al., Chem. Pharm. Bull., 32:692 (1984), each of which is specifically incorporated herein by reference. [0045] Additionally, the present disclosure provides for metabolites of compounds of the disclosure. As used herein, a “metabolite” refers to a product produced through metabolism in the body of a specified compound or salt thereof. Such products can result for example from the oxidation, reduction, hydrolysis, amidation, deamidation, esterification, deesterification, enzymatic cleavage, and the like, of the administered compound. [0046] Metabolite products typically are identified by preparing a radiolabeled (e.g., ¹⁴ C or ³ H) isotope of a compound of the disclosure, administering it parenterally in a detectable dose (e.g., greater than about 0.5 mg/kg) to an animal such as rat, mouse, guinea pig, monkey, or to man, allowing sufficient time for metabolism to occur (typically about 30 seconds to 30 hours) and isolating its conversion products from the urine, blood or other biological samples. These products are easily isolated since they are labeled (others are isolated by the use of antibodies capable of binding epitopes surviving in the metabolite). The metabolite structures are determined in conventional fashion, e.g., by MS, LC/MS or NMR analysis. In general, analysis of metabolites is done in the same way as conventional drug metabolism studies well known to those skilled in the art. The metabolite products, so long as they are not otherwise found in vivo, are useful in diagnostic assays for therapeutic dosing of the compounds of the disclosure. [0047] Certain compounds of the present disclosure can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are intended to be encompassed within the scope of the present disclosure. Certain compounds of the present disclosure can exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present disclosure and are intended to be within the scope of the present disclosure. [0048] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers.” Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers.” Diastereomers are stereoisomers with opposite configuration at one or more chiral centers which are not enantiomers. Stereoisomers bearing one or more asymmetric centers that are non-superimposable mirror images of each other are termed “enantiomers.” When a compound has an asymmetric center, for example, if a carbon atom is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center or centers and is described by the R- and S-sequencing rules of Cahn, Ingold and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. In certain aspects the compound is enriched by at least about 90% by weight with a single diastereomer or enantiomer. In other aspects the compound is enriched by at least about 95%, 98%, or 99% by weight with a single diastereomer or enantiomer. [0049] Certain compounds of the present disclosure possess asymmetric carbon atoms (optical centers) or double bonds; the racemates, diastereomers, geometric isomers, regioisomers and individual isomers (e.g., separate enantiomers) are all intended to be encompassed within the scope of the present disclosure. [0050] The compounds of the present disclosure may also exist in different tautomeric forms, and all such forms are embraced within the scope of the disclosure. The term “tautomer” or “tautomeric form” refers to structural isomers of different energies which are interconvertible via a low energy barrier. For example, proton tautomers (also known as prototropic tautomers) include interconversions via migration of a proton, such as keto-enol and imine-enamine isomerizations. Valence tautomers include interconversions by reorganization of some of the bonding electrons. [0051] Unless otherwise indicated, the term “a compound of the formula” or “a compound of formula” or “compounds of the formula” or “compounds of formula” refers to any compound selected from the genus of compounds as defined by the formula. In some embodiments or aspects, the term also includes a pharmaceutically acceptable salt or ester of any such compound, a stereoisomer, or a tautomer of such compound. [0052] The term “a therapeutically effective amount” of a compound means an amount of compound that is effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated. Determination of a therapeutically effective amount is within the skill in the art. The therapeutically effective amount or dosage of a compound according to this disclosure can vary within wide limits and may be determined in a manner known in the art. Such dosage will be adjusted to the individual requirements in each particular case including the specific compound(s) being administered, the route of administration, the condition being treated, as well as the patient being treated. In general, in the case of oral or parenteral administration to adult humans weighing approximately 70 kg, a daily dosage of about 0.1 mg to about 5,000 mg, 1 mg to about 1,000 mg, or 1 mg to 100 mg may be appropriate, although the lower and upper limits may be exceeded when indicated. The daily dosage can be administered as a single dose or in divided doses, or for parenteral administration, it may be given as continuous infusion. [0053] The term “pharmaceutically acceptable carrier” is intended to include any and all material compatible with pharmaceutical administration including solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and other materials and compounds compatible with pharmaceutical administration. Except insofar as any conventional media or agent is incompatible with a compound of the disclosure, use thereof in the compositions of the disclosure is contemplated. Supplementary active compounds can also be incorporated into the compositions. COMPOUNDS [0054] In some aspects, of the present disclosure, the compounds, or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, are of the following formula (B-1): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: X1 is N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C _1-6 alkyl of R ₅ is optionally substituted with hydroxyl or N(R ^e )(R ^f ), or the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl, provided that X ₃ is CH; X ₂ is N or C-R ₅ , wherein each R ₅ is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ); X3 is N or C-H, provided that, when X3 is N, and R1 is then at least one of X1 and X ₂ is N; R1 is: (i) oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with one or more -C(O)NH ₂ , and L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) N(R ^e )(CN), and L is absent or is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or _(iii) wherein R _a , R _b , and R _c are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH2-O-**, *-O-CH2-**, - CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iv) , wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C _1- 6alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; R ₂ is C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, C _5- 13spirocyclyl, or 5-20 membered heteroaryl, wherein the C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- 13spirocyclyl, or 5-20 membered heteroaryl of R2 is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- ₆ haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), O(R ^e ), and SF ₅ , provided that, when R ₂ is C _1-12 alkyl, wherein the C _1-12 alkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1- ₆ alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), then L is -CH=CH- or -C≡C-; R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), or R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl, provided that X ₃ is CH, or R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl, provided that: (i) when R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), and R _{1 is} and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) when R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, provided that X ₃ is CH, and _{R1 is} and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is absent or is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (iii) when R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, and R R _{1 is} then R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ); R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl; and R ^e and R ^f are, independently of each other and independently at each occurrence, selected from the group consisting of H, cyano, hydroxyl, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl of R ^e and R ^f are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. [0055] In some aspects of the present disclosure, the compounds, or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, are of the following formula (B): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: X ₁ is N or C-R ₅ , wherein each R ₅ is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ), or the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH; X2 is N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH ₂ , N(R ^e )(R ^f ), C _3-10 cycloalkyl, C _1-6 alkoxy, C _6-20 aryl, and C _1-6 alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ); X ₃ is N or C-H, provided that, when X ₃ is N, and R ₁ is then at least one of X ₁ and X is N; 2 R ₁ is: (i) oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C _1-6 alkyl, and L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (ii) N(R ^e )(CN), and L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or _(iii) ^Rc , wherein R _a , R _b , and R _c are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH ₂ -O-**, *-O-CH ₂ -**, - CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iv) , wherein R _d is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C1- ₆ alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; R2 is C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- 13spirocyclyl, or 5-20 membered heteroaryl, wherein the C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, C _5- 13spirocyclyl, or 5-20 membered heteroaryl of R2 is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- ₆ haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), provided that, when R ₂ is C _1-12 alkyl, wherein the C _1-12 alkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is -CH=CH- or -C≡C-; R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), or R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH, or R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, provided that, when: (i) R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), and R _{1 is} and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH, and R _{1 is} and R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _{1- 6} alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), then L is absent or is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iii) R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, and then R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ); R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl; and R ^e and R ^f are, independently of each other and independently at each occurrence, selected from the group consisting of H, cyano, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl of R ^e and R ^f are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. [0056] In embodiments, X1 is N or C-R5, wherein R5 is selected from the group consisting of H, C3-10cycloalkyl and C1-6alkyl, or the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH. [0057] In embodiments, X ₂ is N or C-R ₅ , wherein each R ₅ is independently selected from the group consisting of H, cyano, halo, C(O)NH ₂ , C _1-6 alkoxy, C _6-20 aryl, and C _1-6 alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl. [0058] In embodiments, X ₃ is N or C-H, provided that, when X ₃ is N, and R ₁ is , then at least one of X ₁ and X ₂ is N. [0059] In embodiments, R1 is (i) oxiranyl optionally substituted with one or more C1-6alkyl, and L is absent; or (ii) N(R ^e )(CN), and L is absent; or ( _iii) ^Rc , wherein R _a , R _b , and R _c are each independently selected from the group consisting of H, cyano, C6-20aryl and C1-6alkyl optionally substituted with hydroxyl, and L is absent or is selected from the group consisting of -CH=CH- and *- CH ₂ -O-**, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; or (iv) , wherein R _d is H, and L is -CH=CH-. [0060] In embodiments, R2 is selected from the group consisting of C1-12alkyl, C3- 10cycloalkyl, C6-20aryl, and C5-13spirocyclyl, wherein the C1-12alkyl, C3-10cycloalkyl, C6-20aryl, and C _5-13 spirocyclyl are independently optionally substituted with one or two substituents selected from the group consisting of halo, C1-6alkyl and C1-6haloalkyl, provided that, when R2 is C1-12alkyl, then L is -CH=CH- or -C≡C-. [0061] In embodiments, R ₃ is cyano or C _1-4 alkoxy; or R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH; or R3 is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl. [0062] In embodiments, R4 is H. [0063] In embodiments, R ^e and R ^f are, independently of each other and independently at each occurrence, selected from the group consisting of H and C1-6alkyl. [0064] In some aspects of the present disclosure, the compounds, or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, are of the following formula (I): wherein: X1 and X2 are each independently N or C-R5, wherein R5 is selected from the group consisting of hydrogen, cyano, halo, C(O)NH ₂ , NH(R ^e ), C _1-6 alkyl, C _3-10 cycloalkyl, C _1-6 alkoxy, and C _6-20 aryl, wherein the C1-6alkyl is optionally substituted with hydroxyl; X ₃ is N or CH, provided that, when X ₃ is N, at least one of X ₁ and X ₂ is N; R1 is , wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or , wherein wherein R _d is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; R ₂ is C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, or C _{5- 13} spirocyclyl, wherein the C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6- 20aryl, or C5-13spirocyclyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _{3- 10} cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3- 10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl, provided that, when R2 is C1-12alkyl, wherein the C1-12alkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), L is -CH=CH- or -C≡C-; R ₃ is cyano, C _1-6 alkyl, C _1-4 alkoxy, or C _2-4 alkenyl, wherein the C _2-4 alkenyl is optionally substituted with NH(R ^e ); or R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, provided that X3 is CH; or R3 is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl, provided that: (i) when R ₃ is cyano, C _1-6 alkyl, C _1-4 alkoxy, or C _2-4 alkenyl, wherein the C _2-4 alkenyl is optionally substituted with N(R ^e )(R ^f ), and R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), L is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (ii) when R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, provided that X3 is CH, and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), L is absent or is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iii) when R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), L is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; and R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl. [0065] In certain embodiments, provided herein is a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl. It is to be understood that the “5- membered” size descriptor of the heterocyclyl or heteroaryl formed by joining R ₃ and the R ₅ of X1 refers to the size of the monocyclic ring moiety that is formed by joining R3 and the R5 of X1. Additionally, the 5-membered heterocyclyl or 5-membered heteroaryl formed by joining R3 and the R5 of X1 may be referred to by the chemical name of the 5-membered monocyclic ring moiety that results. For example, if R ₃ is taken together with the R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl, such that the structure of the compound of formula ( , then the ring formation may be described as follows: “R ₃ is taken together with the R ₅ of X ₁ , and the atoms to which they are attached, to form a tetrahydrofuranyl”. [0066] In certain embodiments, provided herein is a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl, provided that X3 is CH. In some embodiments, the 5- membered heterocyclyl is unsubstituted. In certain embodiments, the 5-membered heterocyclyl is substituted with one or more C _1-6 alkyl. In some embodiments, the 5-membered heterocyclyl is substituted with one or more methyl. In some embodiments, the 5-membered heterocyclyl comprises 1, 2, 3, or 4 annular heteroatoms, wherein the heteroatoms are each independently selected from the group consisting of sulfur, oxygen and nitrogen. In some embodiments, the 5- membered heterocyclyl comprises 1 or 2 annular heteroatoms. In other embodiments, the 5- membered heterocyclyl comprises 1 annular heteroatom. [0067] In some embodiments, provided herein is a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl, such that the compound of formula (B-1), formula (B), or formula (I) is a compound of formula (IA), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: [0068] In some embodiments, the compound of formula (IA) is a compound selected from the group consisting of , , , , , an d , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0069] In other embodiments, the compound of formula (IA) is a compound selected from the group consisting of , , and or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0070] In some embodiments, the compound of formula (IA) is a compound selected from the group consisting of or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0071] In some embodiments, provided herein is a compound of formula (IA), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₂ is C-R ₅ . In certain embodiments, the R5 of X2 is cyano. In some embodiments, X2 is C-R5, wherein the R5 of X2 is cyano, L is absent, and R2 is C6-20aryl, wherein the C6-20aryl is optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3- 10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ). In some embodiments, the C6-20aryl of R2 is optionally substituted with one or two C1-6alkyl. In some embodiments, the C1-6alkyl is isopropyl. In certain embodiments, the compound of formula (IA) is a compound of formula (IJ): or a stereosiomer, tautomer, or pharmaceutically acceptable salt thereof. [0072] In some embodiments, the compound of formula (IJ) is selected from the group consisting of and , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (IJ) is selected from the group consisting of and , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0073] In some embodiments, provided herein is a compound of formula (IJ), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C _1-6 alkyl. In some embodiments, R ₁ is oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -C(O)NH2. In some embodiments, R1 is oxetanyl, wherein the oxetanyl is optionally substituted with one or more C _1-6 alkyl. In some embodiments, R ₁ is oxetanyl, wherein the oxetanyl is optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -C(O)NH2. In some embodiments, R1 is oxiranyl, wherein the oxiranyl is unsubstituted. In some embodiments, R ₁ is oxiranyl, wherein the oxiranyl is substituted with one or more C1-6alkyl. In certain embodiments, R1 is oxiranyl, wherein the oxiranyl is substituted with one or more methyl. In some embodiments, R1 is oxetanyl, wherein the oxetanyl is optionally substituted with one or more C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with one or more -C(O)NH ₂ . In some embodiments, R ₁ is oxetanyl, wherein the oxetanyl is optionally substituted with -CH2-CH2-C(O)NH2. [0074] In some embodiments, provided herein is a compound of formula (IJ), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₁ is oxiranyl, wherein the oxiranyl is optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -C(O)NH2. In certain embodiments, the one or more C1- ₆ alkyl is isopropyl. In some embodiments, the compound of formula (B), (IA), or (IJ) is a compound of formula (IK): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein Rg is H or C1- 6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -C(O)NH2. In some embodiments, R _g is H. In other embodiments, R _g is methyl. In other embodiments, R _g is -CH ₂ - CH2-C(O)NH2. [0075] In some embodiments, the compound of formula (IK) is selected from the group , , , , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0076] In some embodiments, provided herein is a compound of formula (IJ), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₁ is N(R ^e )(CN), wherein R ^e is selected from the group consisting of H, cyano, hydroxyl, C1-6alkyl, C2-6alkenyl, C2- 6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3- 20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{1- 6} alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl of R ^e are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. [0077] In certain embodiments, provided herein is a compound of formula (IJ), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (IJ) is a compound of formula (IL): , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. In certain embodiments, R ^e is H. In other embodiments, R ^e is C _1-6 alkyl. In some embodiments, R ^e is methyl. [0078] In certain embodiments, R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl, such that the compound of formula (B-1), formula (B), or formula (I) is a compound of formula (IB), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: [0079] In some embodiments, provided herein is a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heteroaryl, provided that X3 is CH. In some embodiments, the 5-membered heteroaryl is unsubstituted. In certain embodiments, the 5-membered heteroaryl is substituted with one or more C _1-6 alkyl. In some embodiments, the 5-membered heteroaryl is substituted with one or more methyl. In some embodiments, R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heteroaryl, provided that X ₃ is CH, wherein the 5-membered heteroaryl comprises 1, 2, 3, or 4 annular heteroatoms, wherein the heteroatoms are each independently selected from the group consisting of oxygen and nitrogen. In certain embodiments, the 5-membered heteroaryl comprises 1 or 2 annular heteroatoms. [0080] In some embodiments, R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heteroaryl, such that the compound of formula (B-1), formula (B), or formula (I) is a compound of formula (IC), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: [0081] In some embodiments, R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heteroaryl, such that the compound of formula (B-1), formula (B), or formula (I) is a compound of formula (IC-1), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: [0082] In some embodiments, provided is a compound of formula (B-1), formula (B), or formula (I), or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R3 is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl. [0083] In some embodiments, R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C ₆ aryl. In some embodiments, R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C6aryl, such that the compound of formula (B-1), formula (B), or formula (I) is a compound of formula (ID), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: [0084] In some embodiments, R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a 6-membered heteroaryl. In some embodiments, the 6-membered heteroaryl comprises 1, 2, 3, or 4 annular heteroatoms, wherein the heteroatoms are each independently selected from the group consisting of oxygen and nitrogen. In some embodiments, the 6-membered heteroaryl comprises 1 annular heteroatom. [0085] In some embodiments, R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a 6-membered heteroaryl, such that the compound of formula (B-1), formula (B), or formula (I) is a compound of formula (IE), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: [0086] In some embodiments, provided herein is a compound of formula (B-1), formula (B), or formula (I), or a pharmaceutically acceptable salt thereof, wherein R ₄ is H. In other embodiments, R4 is C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl. [0087] In some embodiments, provided herein is a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X3 is CH; L is -CH=CH-; R2 is C3-10cycloalkyl, wherein the C3-10cycloalkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ); R3 is C1-4alkoxy; and R4 is H. In certain embodiments, the compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is a compound of formula (IF), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: [0088] In certain embodiments, the compound of formula (IF) is a compound selected from the group consisting of: , , , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0089] In some aspects of the present disclosure, provided is a compound of formula (B- 1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is . In some embodiments, provided is a compound of formula (B- 1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B-1), formula (B), or formula (I) is a compound of formula (IG): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0090] In embodiments, provided is a compound of formula (IG), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R _a , R _b , and R _c are each H. In other embodiments, provided is a compound of formula (IG), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein one of Ra and Rb is H, the other of Ra and Rb is cyano, and Rc is H. In some embodiments, Ra is H, Rb is cyano, and Rc is H. In other embodiments, provided is a compound of formula (IG), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein Ra is H, Rb is H, and Rc is C6-20aryl. In some embodiments, provided is a compound of formula (IG), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R _a is H, R _b is H, and R _c is C ₆ aryl. In other embodiments, provided is a compound of formula (IG), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein Ra is H, Rb is H, and Rc is C1-6alkyl, wherein the C1-6alkyl is further substituted with hydroxyl. [0091] In some aspects of the present disclosure, provided is a compound of formula (B- 1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is and R2 is C3-10cycloalkyl, wherein the C3-10cycloalkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3- 10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. [0092] In some embodiments, provided is a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B-1), formula (B), or formula (I) is a compound of formula (IH): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0093] In some embodiments, provided is a compound of formula (IH), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein n is 0, 1, 2, 3, or 4, and each R _x , if present, is independently selected from the group consisting of cyano, halo, C1-6alkyl, C1- 6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{1- 6} alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1- 6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. [0094] In some embodiments, provided is a compound of formula (IH), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2, and each R _x , if present, is independently selected from the group consisting of cyano, halo, C1-6alkyl, C1- 6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _{1- 6} alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1- 6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. [0095] In some embodiments, provided is a compound of formula (IH), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R _a , R _b , and R _c of R ₁ are each H, n is 1, and Rx is C1-6haloalkyl. In some embodiments, the C1-6haloalkyl of Rx is CF3. In some embodiments, Ra, Rb, and Rc of R1 are each H, n is 2, and both Rx are halo. In certain embodiments, both R _x are F. [0096] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₁ is N, X ₂ is N, and X ₃ is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X1 is C-R5, wherein R5 is H, X2 is N, and X3 is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X1 is C-R5, wherein R5 is C1-6alkyl, X2 is N, and X ₃ is CH. In still other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X1 is C-R5, wherein R5 is C3- 10cycloalkyl, X2 is N, and X3 is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X1 is N, X2 is C- R5, wherein R5 is H, and X3 is CH. In other embodiments, provided is a compound of formula (B- 1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X1 is N, X2 is C-R5, wherein R5 is cyano, and X3 is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₁ is N, X ₂ is C- R5, wherein R5 is C6-20aryl, and X3 is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₁ is N, X2 is C-R5, wherein R5 is C1-6alkyl substituted with hydroxyl, and X3 is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X1 is N, X2 is C-R5, wherein R5 is C1-6alkoxy, and X3 is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₁ is N, X ₂ is C-R ₅ , wherein R ₅ is C(O)NH2, and X3 is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₁ and X ₂ are both C-R5, wherein each R5 is H, and X3 is CH. In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₁ is C-R5, wherein R5 is H, X2 is C-R5, wherein R5 is halo, and X3 is CH. In still other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₁ is C-R ₅ , wherein R ₅ is H, X ₂ is N, and X ₃ is N. [0097] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is , wherein Ra, Rb, and R _c are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C _1- 6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl wherein the C1- 6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH ₂ -O-**, *-O-CH ₂ -**, - CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule. In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is . In some embodiments, R ^a , R ^b , and R ^c are each H. In other embodiments, R1 is , wherein one of R ^a , R ^b , and R ^c is cyano. In some embodiments, R ₁ is , wherein R ^a is H, R ^b is cyano, and R ^c is H. In other embodiments, R ₁ is , wherein one of R ^a , R ^b , and R ^c is C _6-20 aryl. In some embodiments, R ₁ is , wherein R ^a is H, R ^b is H, and R ^c is C6-20aryl. In other embodiments, R1 is , wherein one of R ^a , R ^b , and R ^c is C1-6alkyl, wherein the C1-6alkyl is further substituted with hydroxyl. In some embodiments, R ₁ is , wherein R ^a is H, R ^b is H, and R ^c is C _1-6 alkyl, wherein the C1-6alkyl is further substituted with hydroxyl. [0098] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is , wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH2-O-**, *-O- CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule. In certain embodiments, R ₁ is , wherein Rd is substituted with C1-6alkyl. [0099] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is and L is absent or is selected from the group consisting of *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule. In some embodiments, R1 is and L is absent. In some embodiments, R ₁ is and L is -CH=CH-. In other embodiments, R ₁ is and L is -*CH2-O-**. In certain embodiments, R1 is and L is -CH=CH-. [0100] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is and L is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule. [0101] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₁ is oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with one or more -C(O)NH2, and L is absent or is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule. In certain embodiments, L is absent. In some embodiments, R1 is oxiranyl, wherein the oxiranyl is optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -C(O)NH ₂ . In some embodiments, R ₁ is oxiranyl, wherein the oxiranyl is unsubstituted. In some embodiments, R1 is oxiranyl, wherein the oxiranyl is substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more - C(O)NH ₂ . In certain embodiments, R ₁ is oxiranyl, wherein the oxiranyl is substituted with one or more methyl. In some embodiments, R1 is . In other embodiments, R1 is . In other [0102] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1 is N(R ^e )(CN), wherein R ^e is selected from the group consisting of H, cyano, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3- ₁₀ cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl- C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl of R ^e are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl, and L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule. In certain embodiments, L is absent. In some embodiments, R ^e is H or C1-6alkyl. In certain embodiments, R ^e is H. In other embodiments, R ^e is C1-6alkyl. In some embodiments, R ^e is methyl. In some embodiments, L is absent and R ^e is H. In other embodiments, L is absent and R ^e is C _1-6 alkyl. In some embodiments, L is absent and R ^e is methyl. [0103] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH-. In certain embodiments, the carbon-carbon double bond is trans, such that the L moiety is . In other embodiments, the carbon-carbon double bond is cis, such that the L moiety is . In certain embodiments, the carbon-carbon double bond is E, such that the L moiety is . In other embodiments, the carbon-carbon double bond is Z, such that the L moiety is . [0104] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₂ is C _3-10 cycloalkyl, wherein the C _3-10 cycloalkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, SF ₅ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3- 10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2- 6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6- ₂₀ aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. In some embodiments, R2 is C3-10cycloalkyl, wherein the C3- ₁₀ cycloalkyl is optionally substituted with one, two, three, or four C _1-6 haloalkyl. In some embodiments, R ₂ is cyclohexyl, wherein the cyclohexyl is optionally substituted with one, two, three, or four CF3. In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₂ is C _3-10 cycloalkyl, wherein the C3-10cycloalkyl is optionally substituted with one, two, three, or four halo. In certain embodiments, R2 is cyclohexyl, wherein the cyclohexyl is optionally substituted with one, two, three, or four F. In other embodiments, R ₂ is cyclobutyl, wherein the cyclobutyl is optionally substituted with one, two, three, or four F. [0105] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₂ is C _5-13 spirocyclyl. In some embodiments, the C _5-13 spirocyclyl is . [0106] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₂ is C _1-12 alkyl, wherein the C _1- 12alkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, SF5, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2- 6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6- ₂₀ aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. In some embodiments, R2 is methyl, wherein the methyl is substituted with cyclopentyl. In some embodiments, other embodiments, R2 is . [0107] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₂ is C _6-20 aryl, wherein the C _6-20 aryl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, SF5, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3- 10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. In certain embodiments, R2 is C6-20aryl, wherein the C6-20aryl is optionally substituted with one, two, three, or four halo. In some embodiments, R ₂ is C _6-20 aryl, wherein the C _6-20 aryl is substituted with one, two, three, or four Cl. In other embodiments, R ₂ is C _6-20 aryl, wherein the C6-20aryl is optionally substituted with one, two, three, or four C1-6alkyl. In some embodiments, R2 is phenyl, wherein the phenyl is substituted with one, two, three, or four isopropyl. In some embodiments, R ₂ is phenyl, wherein the phenyl is substituted with one, two, three, or four SF ₅ . [0108] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₂ is 3-10 membered saturated heterocyclyl, wherein the 3-10 membered saturated heterocyclyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , SF ₅ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C2- 6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3- 20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1- 6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. In some embodiments, R ₂ is tetrahydropyran, wherein the tetrahydropyran is substituted with one, two, three, or four C1-6haloalkyl. In certain embodiments, the C1-6haloalkyl is CF3. [0109] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R2 is tetrahydropyran substituted with CF3, and wherein the stereochemistry of the -L-R2 moiety is (3S,6S), such that the -L-R2 moiety . In other embodiments, R ₂ is tetrahydropyran substituted with CF ₃ , wherein the stereochemistry of the -L-R2 moiety is (3R,6R), such that the -L-R2 moiety is . [0110] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH- and R ₂ is C _{3- 10} cycloalkyl, wherein the R ₂ is C _3-10 cycloalkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- 6haloalkyl, C3-10cycloalkyl, NO2, SF5, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3- ₁₀ cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl- C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. In some embodiments, L is -CH=CH- and R2 is C3-10cycloalkyl, wherein the C3-10cycloalkyl is optionally substituted with one, two, three, or four C1-6haloalkyl. In some embodiments, L is -CH=CH- and R ₂ is cyclohexyl, wherein the cyclohexyl is optionally substituted with one, two, three, or four CF3. In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH- and R ₂ is C _3-10 cycloalkyl, wherein the C3-10cycloalkyl is optionally substituted with one, two, three, or four halo. In certain embodiments, L is -CH=CH- and R2 is cyclohexyl, wherein the cyclohexyl is optionally substituted with one, two, three, or four F. In other embodiments, L is -CH=CH- and R ₂ is cyclobutyl, wherein the cyclobutyl is optionally substituted with one, two, three, or four F. [0111] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is *-CH ₂ -O-** and R ₂ is C _{5- 13} spirocyclyl. In some embodiments, . [0112] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is *-CH ₂ -O-** and R ₂ is C _3- 10cycloalkyl, wherein the R2 is C3-10cycloalkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- ₆ haloalkyl, C _3-10 cycloalkyl, NO ₂ , SF ₅ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3- 10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl- C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. In some embodiments, L is *-CH2-O-** and R2 is C3-10cycloalkyl, wherein the C3-10cycloalkyl is optionally substituted with one, two, three, or four C1-6haloalkyl. In some embodiments, L is *-CH2-O-** and R ₂ is cyclohexyl, wherein the cyclohexyl is optionally substituted with one, two, three, or four CF ₃ . In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is *-CH ₂ -O-** and R ₂ is C _3-10 cycloalkyl, wherein the C _3-10 cycloalkyl is optionally substituted with one, two, three, or four halo. In certain embodiments, L is *-CH2-O-** and R2 is cyclohexyl, wherein the cyclohexyl is optionally substituted with one, two, three, or four F. [0113] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is absent and R2 is C6-20aryl, wherein the C _6-20 aryl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3- 10cycloalkyl, NO2, SF5, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _{3- 10} cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1- 6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. In other embodiments, L is absent and R2 is C6-20aryl, wherein the C6-20aryl is optionally substituted with one, two, three, or four C1- ₆ alkyl. In some embodiments, L is absent and R ₂ is phenyl, wherein the phenyl is substituted with one, two, three, or four isopropyl. In some embodiments, L is absent and R2 is phenyl, wherein the phenyl is substituted with one, two, three, or four SF5. [0114] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH- and R2 is 3-10 membered saturated heterocyclyl, wherein the 3-10 membered saturated heterocyclyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, SF5, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3- 10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. In some embodiments, L is -CH=CH- and R ₂ is tetrahydropyran, wherein the tetrahydropyran is substituted with one, two, three, or four C1-6haloalkyl. In certain embodiments, the C _1-6 haloalkyl is CF ₃ . [0115] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH- and R2 is C6-20aryl, wherein the C _6-20 aryl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3- 10cycloalkyl, NO2, SF5, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3- 10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1- 6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. In certain embodiments, L is - CH=CH- and R2 is C6-20aryl, wherein the C6-20aryl is optionally substituted with one, two, three, or four halo. In some embodiments, L is -CH=CH- and R ₂ is C _6-20 aryl, wherein the C _6-20 aryl is substituted with one, two, three, or four Cl. [0116] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH- or -C≡C-, and R2 is C1-12alkyl, wherein the C1-12alkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _{3- 10} cycloalkyl, NO ₂ , SF ₅ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3- 10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1- ₆ haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. [0117] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH- and R2 is C1-12alkyl, wherein the C _1-12 alkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3- 10cycloalkyl, NO2, SF5, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _{3- 10} cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1- 6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. [0118] In other embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -C≡C-, and R2 is C1-12alkyl, wherein the C1-12alkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _{3- 10} cycloalkyl, NO ₂ , SF ₅ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3- 10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1- ₆ haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. [0119] In certain embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH- and R ₂ is C _1-12 alkyl, wherein the C _1-12 alkyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3- 10cycloalkyl, NO2, SF5, N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3- 10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. In some embodiments, L is-CH=CH- and R2 is methyl, wherein the methyl is substituted with cyclopentyl. In some embodiments, L is -CH=CH- and R2 is . In other embodiments, L is -CH=CH- and R2 is . [0120] In some embodiments, R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C _2-4 alkenyl is optionally substituted with NH(R ^e ). In certain embodiments, R ₃ is C _1-4 alkoxy. In certain embodiments, R3 is methoxy. In other embodiments, R3 is cyano. [0121] In some embodiments, provided is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as applicable, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, provided that X ₃ is CH. [0122] In certain embodiments, R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl, provided that X3 is CH. In certain embodiments, R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl, provided that X ₃ is CH, wherein the 5-membered heterocyclyl comprises 1, 2, 3, or 4 annular heteroatoms, wherein the heteroatoms are each independently selected from the group consisting of oxygen and nitrogen. In certain embodiments, R3 is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl, provided that X ₃ is CH, wherein the 5-membered heterocyclyl comprises a single annular heteroatom, wherein the heteroatom is oxygen or nitrogen. In certain embodiments, R3 is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl, provided that X ₃ is CH, wherein the 5-membered heterocyclyl comprises a single annular heteroatom, wherein the heteroatom is oxygen. [0123] In some embodiments, R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C _2-4 alkenyl is optionally substituted with N(R ^e )(R ^f ); R ₁ is ; R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ); and L is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule. In one embodiment of the foregoing, . In another embodiment of the foregoing, R1 is . [0124] In some embodiments, R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl; X3 is CH; R1 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ); and L is absent or is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule. In one embodiment of the foregoing, . In another embodiment of the foregoing, R1 is . [0125] In some embodiments, R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl; R1 is and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ). In one embodiment of the foregoing, another embodiment of the foregoing, R ₁ . [0126] In some embodiments, provided herein is a compound of formula (B-1), (B), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R4 is H. In other embodiments, R4 is C1- ₆ alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl. [0127] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is C-R ₅ , wherein R ₅ is H; and X ₃ is C-H. [0128] In embodiments, X ₁ is N; X ₂ is C-R ₅ , wherein R ₅ is H; and X ₃ is C-H. [0129] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is N; and X ₃ is C-H. [0130] In embodiments, X1 is N; X2 is N; and X3 is C-H. [0131] In embodiments, R1 is: ^Rc , wherein Ra, Rb, and Rc are each H. [0132] In embodiments, L is -CH=CH-; R ₂ is C _3-10 cycloalkyl optionally substituted with one or two substituents selected from the group consisting of halo, C1-6alkyl, C1-6haloalkyl, O(R ^e ), and SF5. [0133] In embodiments, L is -CH=CH-; R ₂ is C _3-10 cycloalkyl substituted with one or two halo. [0134] In embodiments, L is -CH=CH-; R2 is C3-10cycloalkyl substituted with C1- ₆ haloalkyl. [0135] In embodiments, L is -CH=CH-; R ₂ is cyclohexyl substituted with CF ₃ . [0136] In embodiments, L is -CH=CH-; R2 is cyclohexyl substituted with with one or two fluoro. [0137] In embodiments, R ₃ is C _1-4 alkoxy. [0138] In embodiments, R3 is methoxy. [0139] In embodiments, R4 is H. [0140] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is C-R ₅ , wherein R ₅ is H; X ₃ is R _a C-H; R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H; L is -CH=CH-; R ₂ is C _3-10 cycloalkyl substituted with C1-6haloalkyl; R3 is C1-4alkoxy; and R4 is H. [0141] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is C-R ₅ , wherein R ₅ is H; X ₃ is C-H; R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H; L is -CH=CH-; R ₂ is cyclohexyl substituted with CF3; R3 is methoxy; and R4 is H. [0142] In embodiments, X1 is C-R5, wherein R5 is H; X2 is C-R5, wherein R5 is H; X3 is C-H; R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H; L is -CH=CH-; R ₂ is C _3-10 cycloalkyl substituted with one or two halo; R3 is C1-4alkoxy; and R4 is H. [0143] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is C-R ₅ , wherein R ₅ is H; X ₃ is R _a C-H; R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H; L is -CH=CH-; R ₂ is C _3-10 cycloalkyl substituted with one or two fluoro; R3 is methoxy; and R4 is H. [0144] In embodiments, X1 is N; X2 is C-R5, wherein R5 is H; X3 is C-H; R1 is: ^Rc , wherein R _a , R _b , and R _c are each H; L is -CH=CH-; R ₂ is C _3-10 cycloalkyl substituted with C _1- 6haloalkyl; R3 is C1-4alkoxy; and R4 is H. [0145] In embodiments, X1 is N; X2 is C-R5, wherein R5 is H; X3 is C-H; R1 is: ^Rc , wherein R _a , R _b , and R _c are each H; L is -CH=CH-; R ₂ is cyclohexyl substituted with CF ₃ ; R ₃ is methoxy; and R ₄ is H. R _a R _b [0146] In embodiments, X1 is N; X2 is C-R5, wherein R5 is H; X3 is C-H; R1 is: ^Rc , wherein Ra, Rb, and Rc are each H; L is -CH=CH-; R2 is C3-10cycloalkyl substituted with one or two halo; R ₃ is C _1-4 alkoxy; and R ₄ is H. R _a R _b [0147] In embodiments, X ₁ is N; X ₂ is C-R ₅ , wherein R ₅ is H; X ₃ is C-H; R ₁ is: ^Rc , wherein Ra, Rb, and Rc are each H; L is -CH=CH-; R2 is C3-10cycloalkyl substituted with one or two fluoro; R ₃ is methoxy; and R ₄ is H. R _a [0148] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is N; X ₃ is C-H; R ₁ is: ^Rc , wherein Ra, Rb, and Rc are each H; L is -CH=CH-; R2 is C3-10cycloalkyl substituted with C1- 6haloalkyl; R3 is C1-4alkoxy; and R4 is H. [0149] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is N; X ₃ is C-H; R ₁ is: ^Rc , wherein Ra, Rb, and Rc are each H; L is -CH=CH-; R2 is cyclohexyl substituted with CF3; R3 is methoxy; and R ₄ is H. R _a [0150] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is N; X ₃ is C-H; R ₁ is: ^Rc , wherein Ra, Rb, and Rc are each H; L is -CH=CH-; R2 is C3-10cycloalkyl substituted with one or two halo; R ₃ is C _1-4 alkoxy; and R ₄ is H. [0151] In embodiments, X ₁ is C-R ₅ , wherein R ₅ is H; X ₂ is N; X ₃ is C-H; R ₁ is: ^Rc , wherein Ra, Rb, and Rc are each H; L is -CH=CH-; R2 is C3-10cycloalkyl substituted with one or two fluoro; R3 is methoxy; and R4 is H. R _a [0152] In embodiments, X1 is N; X2 is N; X3 is C-H; R1 is: ^Rc , wherein Ra, Rb, and R _c are each H; L is -CH=CH-; R ₂ is C _3-10 cycloalkyl substituted with C _1-6 haloalkyl; R ₃ is C _1- 4alkoxy; and R4 is H. [0153] In embodiments, X1 is N; X2 is N; X3 is C-H; R1 is: ^Rc , wherein Ra, Rb, and R _c are each H; L is -CH=CH-; R ₂ is C _3-10 cycloalkyl substituted with CF ₃ ; R ₃ is methoxy; and R4 is H. [0154] In embodiments, X1 is N; X2 is N; X3 is C-H; R1 is: ^Rc , wherein Ra, Rb, and R _c are each H; L is -CH=CH-; R ₂ is C _3-10 cycloalkyl substituted with one or two halo; R ₃ is C _{1- 4} alkoxy; and R ₄ is H. R _a [0155] In embodiments, X1 is N; X2 is N; X3 is C-H; R1 is: ^Rc , wherein Ra, Rb, and Rc are each H; L is -CH=CH-; R2 is C3-10cycloalkyl substituted with one or two fluoro; R3 is methoxy; and R ₄ is H. [0156] In embodiments, L is absent; and R2 is C6-20aryl optionally substituted with one or two substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, SF5, and O(R ^e ), wherein R ^e is C _1-6 alkyl optionally substituted with one or more halo. [0157] In embodiments, L is absent; and R ₂ is C _6-20 aryl substituted with C _1-6 alkyl. [0158] In embodiments, L is absent; and R2 is phenyl substituted with C1-6alkyl. [0159] In embodiments, L is absent; and R ₂ is phenyl substituted with isopropyl. [0160] In embodiments, X ₁ is N; X ₂ is C-R ₅ , wherein R ₅ is H or fluoro; X ₃ is C-H; R ₁ is: R _c , wherein Ra, Rb, and Rc are each H; L is absent; and R2 is C6-20aryl optionally substituted with one or two substituents selected from the group consisting of C1-6alkyl, C1- ₆ haloalkyl, SF ₅ , and O(R ^e ), wherein R ^e is C _1-6 alkyl optionally substituted with one or more halo; R3 is C1-4alkoxy; and R4 is H. [0161] In embodiments, X1 is N; X2 is C-R5, wherein R5 is H or fluoro; X3 is C-H; R1 is: R _c , wherein R _a , R _b , and R _c are each H; L is absent; and R ₂ is C _6-20 aryl substituted with C _1-6 alkyl; R ₃ is C _1-4 alkoxy; and R ₄ is H. [0162] In embodiments, X1 is N; X2 is C-R5, wherein R5 is H or fluoro; X3 is C-H; R1 is: R _c , wherein Ra, Rb, and Rc are each H; L is absent; and R2 is phenyl substituted with isopropyl; R ₃ is methoxy; and R ₄ is H. [0163] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C _1-6 alkyl. [0164] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C _1-6 alkyl. [0165] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C _1-6 alkyl. [0166] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl. [0167] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; and X3 is C-H. [0168] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; and X3 is C-H. [0169] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; and X3 is C-H. [0170] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X2 is C-R5, wherein R5 is H or cyano; and X3 is C-H. [0171] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H, cyano, halo or C1-6alkyl optionally substituted with hydroxyl; and X3 is C-H. [0172] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H, cyano, halo or C1-6alkyl optionally substituted with hydroxyl; and X ₃ is C-H. [0173] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is H, cyano, halo or C _1-6 alkyl optionally substituted with hydroxyl; and X ₃ is C-H. [0174] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X ₂ is C-R ₅ , wherein R ₅ is H, cyano, halo or C _1-6 alkyl optionally substituted with hydroxyl; and X3 is C-H. [0175] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H, cyano, halo or C1-6alkyl R _a optionally substituted with hydroxyl; X3 is C-H; and R1 is: ^Rc , wherein Ra, Rb, and Rc are each H. [0176] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is H, cyano, halo or C _1-6 alkyl optionally substituted with hydroxyl; X ₃ is C-H; and R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H. [0177] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is H, cyano, halo or C _1-6 alkyl optionally substituted with hydroxyl; X ₃ is C-H; and R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H. [0178] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one R _a methyl; and R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H. [0179] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H, cyano, halo or C1-6alkyl optionally substituted with hydroxyl; X3 is C-H; R1 is: ^Rc , wherein Ra, Rb, and Rc are each H; and R ₄ is H or C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl. [0180] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H, cyano, halo or C1-6alkyl optionally substituted with hydroxyl; X ₃ is C-H; R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H; and R ₄ is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl. [0181] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H, cyano, halo or C1-6alkyl optionally substituted with hydroxyl; X3 is C-H; and R1 is: ^Rc , wherein Ra, Rb, and Rc are each H; and R4 is H or C1- ₆ alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl. [0182] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X ₂ is C-R ₅ , wherein R ₅ is H, cyano, halo or C _1-6 alkyl optionally substituted with hydroxyl; X ₃ is C-H; R ₁ is: ^Rc , wherein R _a , R _b , and R _c are each H; and R ₄ is H or C _1-6 alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl. [0183] In embodiments, R ₁ is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ . [0184] In embodiments, R1 is N(R ^e )(CN). [0185] In embodiments, , wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, cyano, C _1-6 alkyl, C _6-20 aryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H. [0186] In embodiments, , wherein R _d is H. [0187] In embodiments, R ₁ is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH2; and R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl. [0188] In embodiments, R ₁ is N(R ^e )(CN); and R ₄ is H or C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl. [0189] In embodiments, , wherein R _a , R _b , and R _c are each independently selected from the group consisting of H, cyano, C1-6alkyl, C6-20aryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H; and R ₄ is H or C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl. [0190] In embodiments, , wherein Rd is H; and R4 is H or C1-6alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl. [0191] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2. [0192] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2. [0193] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; and R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ . [0194] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X ₂ is C-R ₅ , wherein R ₅ is H or cyano; X ₃ is C-H; and R ₁ is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ . [0195] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is absent; and R ₂ is C _6-20 aryl substituted with C _1-6 alkyl. [0196] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is absent; and R ₂ is C _6-20 aryl substituted with C _1-6 alkyl. [0197] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is H or cyano; X ₃ is C-H; and R ₁ is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is absent; and R ₂ is C _6- 20aryl substituted with C1-6alkyl. [0198] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; and R1 is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is absent; and R2 is C6-20aryl substituted with C _1-6 alkyl. [0199] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is cyano; X ₃ is C-H; R ₁ is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is absent; and R2 is phenyl substituted with C1-6alkyl. [0200] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is absent; and R2 is phenyl substituted with C1-6alkyl. [0201] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is H or cyano; X ₃ is C-H; and R ₁ is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is absent; and R2 is phenyl substituted with C1-6alkyl. [0202] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; and R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is absent; and R ₂ is phenyl substituted with C1-6alkyl. [0203] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is cyano; X ₃ is C-H; R ₁ is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is absent; and R ₂ is phenyl substituted with isopropyl. [0204] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is absent; and R2 is phenyl substituted with isopropyl. [0205] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; and R1 is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is absent; and R2 is phenyl substituted with isopropyl. [0206] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; and R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is absent; and R ₂ is phenyl substituted with isopropyl. [0207] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is -CH=CH- ; R ₂ is C _3-10 cycloalkyl optionally substituted with one or two substituents selected from the group consisting of halo, C1-6alkyl, C1-6haloalkyl, O(R ^e ), and SF5. [0208] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is -CH=CH- ; R ₂ is C _3-10 cycloalkyl optionally substituted with one or two substituents selected from the group consisting of halo, C1-6alkyl, C1-6haloalkyl, O(R ^e ), and SF5. [0209] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is H or cyano; X ₃ is C-H; and R ₁ is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is -CH=CH-; R ₂ is C _3- 10cycloalkyl optionally substituted with one or two substituents selected from the group consisting of halo, C _1-6 alkyl, C _1-6 haloalkyl, O(R ^e ), and SF ₅ . [0210] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; and R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is -CH=CH-; R ₂ is C _3-10 cycloalkyl optionally substituted with one or two substituents selected from the group consisting of halo, C1- 6alkyl, C1-6haloalkyl, O(R ^e ), and SF5. [0211] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is cyano; X ₃ is C-H; R ₁ is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is -CH=CH- ; R2 is C3-10cycloalkyl substituted with one or two substituents selected from the group consisting of halo. [0212] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is -CH=CH- ; R2 is C3-10cycloalkyl substituted with one or two substituents selected from the group consisting of halo. [0213] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; and R1 is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is -CH=CH-; R2 is C3- ₁₀ cycloalkyl substituted with one or two substituents selected from the group consisting of halo. [0214] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X ₂ is C-R ₅ , wherein R ₅ is H or cyano; X ₃ is C-H; and R ₁ is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is -CH=CH-; R2 is C3-10cycloalkyl substituted with one or two substituents selected from the group consisting of halo. [0215] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is cyano; X3 is C-H; R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is -CH=CH- ; R ₂ is cyclohexyl substituted with with one or two fluoro. [0216] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl optionally substituted with one or more C _1-6 alkyl; X ₂ is C-R ₅ , wherein R ₅ is H or cyano; X ₃ is C-H; R ₁ is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is -CH=CH- ; R2 is cyclohexyl substituted with with one or two fluoro. [0217] In embodiments, X ₁ is C-R ₅ , wherein the R ₅ of X ₁ is taken together with R ₃ , and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one or more C1-6alkyl; X2 is C-R5, wherein R5 is H or cyano; X3 is C-H; and R1 is oxiranyl optionally substituted with C _1-6 alkyl further optionally substituted with -C(O)NH ₂ ; L is -CH=CH-; R ₂ is cyclohexyl substituted with with one or two fluoro. [0218] In embodiments, X1 is C-R5, wherein the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a tetrahydrofuranyl optionally substituted with one methyl; X ₂ is C-R ₅ , wherein R ₅ is H or cyano; X ₃ is C-H; and R ₁ is oxiranyl optionally substituted with C1-6alkyl further optionally substituted with -C(O)NH2; L is -CH=CH-; R2 is cyclohexyl substituted with with one or two fluoro. [0219] In embodiments, L is *-CH ₂ -O-**, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; and R2 is C3- 10cycloalkyl substituted with C1-6haloalkyl. [0220] In embodiments, L is *-CH ₂ -O-**, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; and R ₂ is cyclohexyl substituted with CF3. [0221] In embodiments, L is *-CH2-O-**, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; and R ₂ is C _3- 10cycloalkyl substituted with one or two halo. [0222] In embodiments, L is *-CH2-O-**, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; and R ₂ is cyclohexyl substituted with one or two fluoro. [0223] In embodiments, L is *-CH2-O-**, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; and R2 is C5- ₁₃ spirocyclyl. [0224] In embodiments, L is *-CH ₂ -O-**, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; and R2 is spirohexane. [0225] In embodiments, L is -CH=CH-, and R ₂ is C _1-12 alkyl. [0226] In embodiments, L is -CH=CH-, and R2 is C1-12alkyl substituted with C3- 10cycloalkyl. [0227] In embodiments, L is -CH=CH-, and R ₂ is methylene substituted with cyclopentyl. [0228] In embodiments, L is -CH=CH-, and R2 is 3-10 membered saturated heterocyclyl substituted with C1-6haloalkyl. [0229] In embodiments, L is -CH=CH-, and R ₂ is tetrahydropyran substituted with CF ₃ . [0230] In some aspects, a compound as described herein, such as a compound of formula (B-1), formula (B), or formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, is selected from the compounds listed in Table 1 below, including racemic mixtures, resolved isomers, tautomers, and pharmaceutically acceptable salts thereof: Table 1

[0231] Provided herein is a compound selected from the group consisting of: 3-cyano-N-(5-methoxy-4-(2-(4-(trifluoromethyl)cyclohexyl)vin yl)pyridin-2-yl)acrylamide; N-(6-methoxy-5-(2-(4-(trifluoromethyl)cyclohexyl)vinyl)pyrid in-3-yl)acrylamide; N-(6-methoxy-5-(2-(4-(trifluoromethyl)cyclohexyl)vinyl)pyrid in-3-yl)but-2-ynamide; N-(5-(2-(4,4-difluorocyclohexyl)vinyl)-6-methoxypyridin-3-yl )acrylamide; N-(6-methoxy-5-(2-(4-(trifluoromethyl)cyclohexyl)vinyl)pyrid azin-3-yl)acrylamide; N-(5-methoxy-4-(2-(4-(trifluoromethyl)cyclohexyl)vinyl)pyrid in-2-yl)acrylamide; N-(4-(2-(4,4-difluorocyclohexyl)vinyl)-5-methoxypyridin-2-yl )acrylamide; N-(5-methoxy-6-methyl-4-(2-(4-(trifluoromethyl)cyclohexyl)vi nyl)pyridin-2-yl)acrylamide; N-(6-methoxy-5-(((4-(trifluoromethyl)cyclohexyl)oxy)methyl)p yridin-3-yl)acrylamide; N-(5-(((4,4-difluorocyclohexyl)oxy)methyl)-6-methoxypyridin- 3-yl)acrylamide; N-(6-methoxy-5-((spiro[2.3]hexan-5-yloxy)methyl)pyridin-3-yl )acrylamide; N-(6-cyclopropyl-5-methoxy-4-(2-(4-(trifluoromethyl)cyclohex yl)vinyl)pyridin-2-yl)acrylamide; N-(2-cyano-6-methoxy-5-(2-(4-(trifluoromethyl)cyclohexyl)vin yl)pyridin-3-yl)acrylamide; N-(3-(3-cyclopentylprop-1-en-1-yl)-4-methoxyphenyl)acrylamid e; N-(2-hydroxyethyl)-N-(5-methoxy-4-(2-(4-(trifluoromethyl)cyc lohexyl)vinyl)pyridin-2- yl)acrylamide; N-(4-fluoro-4'-isopropyl-6-methoxy-[1,1'-biphenyl]-3-yl)acry lamide; N-(7-(4-chlorostyryl)-2,3-dihydrobenzofuran-5-yl)acrylamide; N-(6-methoxy-5-(4-methylpent-1-en-1-yl)pyridin-3-yl)acrylami de; N-(5-(2-(3,3-difluorocyclobutyl)vinyl)-6-methoxypyridin-3-yl )acrylamide; N-(5-(2-(4,4-difluorocyclohexyl)vinyl)-6-methoxypyridin-3-yl )-2-phenylacrylamide; 3-cyano-N-(5-(2-(4,4-difluorocyclohexyl)vinyl)-6-methoxypyri din-3-yl)acrylamide; N-(4-methoxy-3-(2-(4-(trifluoromethyl)cyclohexyl)vinyl)pheny l)acrylamide; N-(3-(2-(4,4-difluorocyclohexyl)vinyl)-4-methoxyphenyl)acryl amide; N-(6-methoxy-2-phenyl-5-(2-(4-(trifluoromethyl)cyclohexyl)vi nyl)pyridin-3-yl)acrylamide; N-(2-(hydroxymethyl)-6-methoxy-5-(2-(4-(trifluoromethyl)cycl ohexyl)vinyl)pyridin-3- yl)acrylamide; N-(2,6-dimethoxy-5-(2-(4-(trifluoromethyl)cyclohexyl)vinyl)p yridin-3-yl)acrylamide; N-(4-(2-(4,4-difluorocyclohexyl)vinyl)-5-methoxypyrimidin-2- yl)acrylamide; 3-acrylamido-6-methoxy-5-(2-(4-(trifluoromethyl)cyclohexyl)v inyl)picolinamide; N-(5-cyano-4-(2-(4,4-difluorocyclohexyl)vinyl)pyridin-2-yl)a crylamide; 2-(hydroxymethyl)-N-(6-methoxy-5-(2-(4-(trifluoromethyl)cycl ohexyl)vinyl)pyridin-3- yl)acrylamide; N-(6-cyano-5-(2-(4-(trifluoromethyl)cyclohexyl)vinyl)pyridin -3-yl)-2- (hydroxymethyl)acrylamide; N-(7-(2-(4,4-difluorocyclohexyl)vinyl)-2,3-dihydrobenzofuran -5-yl)acrylamide; N-(7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)acrylami de; N-(7-(((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-2,3-dihydr obenzofuran-5-yl)acrylamide; N-(7-(2-(4,4-difluorocyclohexyl)vinyl)-2-methyl-2,3-dihydrob enzofuran-5-yl)acrylamide; N-(7-(2-(4,4-difluorocyclohexyl)vinyl)-2,3-dihydrobenzofuran -5-yl)-N-(2- hydroxyethyl)acrylamide; N-(7-(2-(4,4-difluorocyclohexyl)vinyl)-4-fluoro-2,3-dihydrob enzofuran-5-yl)acrylamide; N-(5-((4-(trifluoromethyl)cyclohexyl)oxy)quinolin-3-yl)acryl amide; N-(5-((4-(trifluoromethyl)cyclohexyl)oxy)-1,6-naphthyridin-3 -yl)acrylamide; N-(7-(2-(4,4-difluorocyclohexyl)vinyl)benzo[d]oxazol-5-yl)ac rylamide; N-(5-(4-isopropylphenyl)-6-methoxypyridin-3-yl)acrylamide; N-(6-methoxy-5-(2-(6-(trifluoromethyl)tetrahydro-2H-pyran-3- yl)vinyl)pyridin-3-yl)acrylamide; N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl) -2-methyloxirane-2- carboxamide; N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl) -2-methyloxirane-2- carboxamide; N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl) oxirane-2-carboxamide; N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl) oxirane-2-carboxamide; 3-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl) -1-cyano-1-methylurea; 1-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl) -3-cyano-1-methylurea; N-(4-cyano-7-(4-(1,1-difluoroethyl)phenyl)-2,3-dihydrobenzof uran-5-yl)oxirane-2-carboxamide; N-(4-cyano-7-(4-(1,1-difluoroethyl)phenyl)-2,3-dihydrobenzof uran-5-yl)oxirane-2-carboxamide; N-(4-cyano-7-(4-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofu ran-5-yl)oxirane-2-carboxamide; N-(4-cyano-7-(4-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofu ran-5-yl)oxirane-2-carboxamide; N-(4-(hydroxymethyl)-7-(4-(trifluoromethoxy)phenyl)-2,3-dihy drobenzofuran-5-yl)acrylamide; 2-(3-amino-3-oxopropyl)-N-(4-cyano-7-(4-isopropylphenyl)-2,3 -dihydrobenzofuran-5- yl)oxirane-2-carboxamide; N-[4-(hydroxymethyl)-7-[4-(pentafluoro-6-sulfanyl)phenyl]-2, 3-dihydrobenzofuran-5-yl]prop-2- enamide; and N-(7-cyano-4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazol-6-y l)acrylamide, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. Also provided herein are, where applicable, any and all stereoisomers of the compounds depicted herein, including geometric isomers (e.g., cis/trans isomers or E/Z isomers), enantiomers, diastereomers, or mixtures thereof in any ratio, including racemic mixtures. [0232] In some aspects, the compounds of the disclosure are isotopically labeled by having one or more atoms therein replaced by an atom having a different atomic mass or mass number. Such isotopically-labeled (i.e., radiolabeled) compounds of formula (B-1), formula (B), or formula (I) are considered to be within the scope of this disclosure. Examples of isotopes that can be incorporated into the compounds of formula (B-1), formula (B), or formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine, and iodine, such as, but not limited to, ² H, ³ H, ¹¹ C, ¹³ C, ¹⁴ C, ¹³ N, ¹⁵ N, ¹⁵ O, ¹⁷ O, ¹⁸ O, ³¹ P, ³² P, ³⁵ S, ¹⁸ F, ³⁶ Cl, ¹²³ I, and ¹²⁵ I, respectively. These isotopically-labeled compounds would be useful to help determine or measure the effectiveness of the compounds, by characterizing, for example, the site or mode of action, or binding affinity to TEAD. Certain isotopically-labeled compounds of formula (B-1), formula (B), or formula (I), for example, those incorporating a radioactive isotope, are useful in drug and/or substrate tissue distribution studies. The radioactive isotopes tritium, i.e. ³ H, and carbon-14, i.e., ¹⁴ C, are particularly useful for this purpose in view of their ease of incorporation and ready means of detection. For example, a compound of formula (B-1), formula (B), or formula (I) can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99 percent of a given isotope. [0233] Substitution with heavier isotopes such as deuterium, i.e. ² H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements. [0234] Substitution with positron emitting isotopes, such as ¹¹ C, ¹⁸ F, ¹⁵ O and ¹³ N, can be useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically-labeled compounds of formula (B-1), formula (B), or formula (I) can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the Examples as set out below using an appropriate isotopically- labeled reagent in place of the non-labeled reagent previously employed. [0235] Also provided herein is a pharmaceutically acceptable salt or ester of any compound provided herein, as well as a stereoisomer, a geometric isomer, a tautomer, a solvate, a metabolite, an isotope or a prodrug of such compound or a pharmaceutically acceptable salt of such compound. PHARMACEUTICAL COMPOSITIONS AND ADMINISTRATION [0236] In addition to one or more of the compounds provided above (including stereoisomers, geometric isomers, tautomers, solvates, metabolites, isotopes, pharmaceutically acceptable salts, or prodrugs thereof), the disclosure also provides for compositions and medicaments comprising a compound of the present disclosure or an embodiment or aspect thereof and at least one pharmaceutically acceptable carrier. The compositions of the disclosure can be used to selectively inhibit TEAD in patients (e.g., humans). [0237] In one aspect, the disclosure provides for pharmaceutical compositions or medicaments comprising a compound of the disclosure (or embodiments and aspects thereof including stereoisomers, geometric isomers, tautomers, solvates, metabolites, isotopes, pharmaceutically acceptable salts, and prodrugs) and a pharmaceutically acceptable carrier, diluent or excipient. In another aspect, the disclosure provides for preparing compositions (or medicaments) comprising compounds of the disclosure. In another aspect, the disclosure provides for administering compounds of the disclosure and compositions comprising compounds of the disclosure to a patient (e.g., a human patient) in need thereof. [0238] The carrier can be selected from the various oils including those of petroleum, animal, vegetable or synthetic origin, e.g., peanut oil, soybean oil, mineral oil, sesame oil, and the like. Water, saline, aqueous dextrose, and glycols are preferred liquid carriers, particularly (when isotonic with the blood) for injectable solutions. For example, formulations for intravenous administration comprise sterile aqueous solutions of a compound of the disclosure which are prepared by dissolving solid compounds of the disclosure in water to produce an aqueous solution, and rendering the solution sterile. Suitable pharmaceutical excipients include starch, cellulose, talc, glucose, lactose, talc, gelatin, malt, rice, flour, chalk, silica, magnesium stearate, sodium stearate, glycerol monostearate, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol, and the like. The compositions may be subjected to conventional pharmaceutical additives such as preservatives, stabilizing agents, wetting or emulsifying agents, salts for adjusting osmotic pressure, buffers and the like. Suitable pharmaceutical carriers and their formulation are described in Remington's Pharmaceutical Sciences by E. W. Martin. Such compositions will, in any event, contain an effective amount of a compound of the disclosure together with a suitable carrier so as to prepare the proper dosage form for proper administration to the recipient. [0239] Compositions are formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners. The effective amount of the compound to be administered will be governed by such considerations, and is the minimum amount necessary to inhibit TEAD activity as required to prevent or treat the undesired disease or disorder, such as for example, pain. For example, such amount may be below the amount that is toxic to normal cells, or the mammal as a whole. [0240] In one example, the therapeutically effective amount of the compound of the disclosure administered parenterally per dose will be in the range of about 0.01-100 mg/kg, alternatively about e.g., 0.1 to 20 mg/kg of patient body weight per day, with the typical initial range of compound used being 0.3 to 15 mg/kg/day. The daily does is, in certain aspects, given as a single daily dose or in divided doses two to six times a day, or in sustained release form. In the case of a 70 kg adult human, the total daily dose will generally be from about 7 mg to about 1,400 mg. This dosage regimen may be adjusted to provide the optimal therapeutic response. The compounds may be administered on a regimen of 1 to 4 times per day, preferably once or twice per day. [0241] The compounds of the present disclosure may be administered in any convenient administrative form, e.g., tablets, powders, capsules, solutions, dispersions, suspensions, syrups, sprays, suppositories, gels, emulsions, patches, etc. Such compositions may contain components conventional in pharmaceutical preparations, e.g., diluents, carriers, pH modifiers, sweeteners, bulking agents, and further active agents. [0242] The compositions comprising compounds of the disclosure (or embodiments or aspects thereof including stereoisomers, geometric isomers, tautomers, solvates, metabolites, isotopes, pharmaceutically acceptable salts, and prodrugs thereof) are normally formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition. A typical formulation is prepared by mixing a compound of the present disclosure and a diluent, carrier or excipient. Suitable diluents, carriers and excipients are well known to those skilled in the art and are described in detail in, e.g., Ansel, Howard C., et al., Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lippincott, Williams & Wilkins, 2004; Gennaro, Alfonso R., et al. Remington: The Science and Practice of Pharmacy. Philadelphia: Lippincott, Williams & Wilkins, 2000; and Rowe, Raymond C. Handbook of Pharmaceutical Excipients. Chicago, Pharmaceutical Press, 2005. The formulations may also include one or more buffers, stabilizing agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, glidants, processing aids, colorants, sweeteners, perfuming agents, flavoring agents, diluents and other known additives to provide an elegant presentation of the drug (i.e., a compound of the present disclosure or pharmaceutical composition thereof) or aid in the manufacturing of the pharmaceutical product (i.e., medicament). Suitable carriers, diluents and excipients are well known to those skilled in the art and include buffers such as phosphate, citrate and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and/or non-ionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG). An active pharmaceutical ingredient of the disclosure (e.g., a compound of formula (B-1), formula (B), or formula (I), or an embodiment or aspect thereof) can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano- particles and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington: The Science and Practice of Pharmacy: Remington the Science and Practice of Pharmacy (2005) 21 ^st Edition, Lippincott Williams & Wilkins, Philadelphia, PA. The particular carrier, diluent or excipient used will depend upon the means and purpose for which a compound of the present disclosure is being applied. Solvents are generally selected based on solvents recognized by persons skilled in the art as safe (GRAS) to be administered to a mammal. In general, safe solvents are non-toxic aqueous solvents such as water and other non-toxic solvents that are soluble or miscible in water. Suitable aqueous solvents include water, ethanol, propylene glycol, polyethylene glycols (e.g., PEG 400, PEG 300), etc. and mixtures thereof. [0243] Sustained-release preparations of a compound of the disclosure (e.g., compound of formula (B-1), formula (B), or formula (I), or an embodiment or aspect thereof) can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing a compound of formula (B-1), formula (B), or formula (I), or an embodiment or aspect thereof, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinyl alcohol)), polylactides (U.S. Patent No. 3,773,919), copolymers of L-glutamic acid and gamma-ethyl-L-glutamate (Sidman et al., Biopolymers 22:547, 1983), non-degradable ethylene-vinyl acetate (Langer et al., J. Biomed. Mater. Res.15:167, 1981), degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate) and poly-D-(-)-3-hydroxybutyric acid (EP 133,988A). Sustained release compositions also include liposomally entrapped compounds, which can be prepared by methods known per se (Epstein et al., Proc. Natl. Acad. Sci. U.S.A.82:3688, 1985; Hwang et al., Proc. Natl. Acad. Sci. U.S.A.77:4030, 1980; U.S. Patent Nos.4,485,045 and 4,544,545; and EP 102,324A). Ordinarily, the liposomes are of the small (about 200-800 Angstroms) unilamelar type in which the lipid content is greater than about 30 mol % cholesterol, the selected proportion being adjusted for the optimal therapy. [0244] In one example, compounds of the disclosure or an embodiment or aspect thereof may be formulated by mixing at ambient temperature at the appropriate pH, and at the desired degree of purity, with physiologically acceptable carriers, i.e., carriers that are non-toxic to recipients at the dosages and concentrations employed into a galenical administration form. The pH of the formulation depends mainly on the particular use and the concentration of compound, but preferably ranges anywhere from about 3 to about 8. In one example, a compound of the disclosure (or an embodiment or aspect thereof) is formulated in an acetate buffer, at pH 5. In another aspect, the compounds of the disclosure or an embodiment thereof are sterile. The compound may be stored, for example, as a solid or amorphous composition, as a lyophilized formulation or as an aqueous solution [0245] Formulations of a compound of the disclosure suitable for oral administration can be prepared as discrete units such as pills, capsules, cachets or tablets each containing a predetermined amount of a compound of the disclosure. [0246] Compressed tablets can be prepared by compressing in a suitable machine a compound of the disclosure in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active or dispersing agent. Molded tablets can be made by molding in a suitable machine a mixture of a powdered compound of the disclosure moistened with an inert liquid diluent. The tablets can optionally be coated or scored and optionally are formulated so as to provide slow or controlled release of a compound of the disclosure therefrom. [0247] Tablets, troches, lozenges, aqueous or oil suspensions, dispersible powders or granules, emulsions, hard or soft capsules, e.g., gelatin capsules, syrups or elixirs can be prepared for oral use. Formulations of a compound of the disclosure intended for oral use can be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions can contain one or more agents including sweetening agents, flavoring agents, coloring agents and preserving agents, in order to provide a palatable preparation. Tablets containing a compound of the disclosure in admixture with non-toxic pharmaceutically acceptable excipient which are suitable for manufacture of tablets are acceptable. These excipients can be, for example, inert diluents, such as calcium or sodium carbonate, lactose, calcium or sodium phosphate; granulating and disintegrating agents, such as maize starch, or alginic acid; binding agents, such as starch, gelatin or acacia; and lubricating agents, such as magnesium stearate, stearic acid or talc. Tablets can be uncoated or can be coated by known techniques including microencapsulation to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate alone or with a wax can be employed. [0248] An example of a suitable oral administration form is a tablet containing about 0.1 mg, about 1 mg, about 5 mg, about 10 mg, about 25 mg, about 30 mg, about 50 mg, about 80 mg, about 100 mg, about 150 mg, about 250 mg, about 300 mg and about 500 mg of the compounds (or an embodiment or aspect thereof) of the disclosure compounded with a filler (e.g., lactose, such as about 90-30 mg anhydrous lactose), a disintegrant (e.g, croscarellose, such as about 5-40mg sodium croscarmellose), a polymer (e.g. polyvinylpyrrolidone (PVP), a cellulose (e.g., hydroxypropylmethyl cellulose (HPMC), and/or copovidone, such as about 5-30 mg PVP, HPMC or copovidone), and a lubricant (e.g., magnesium stearate, such as about 1-10 mg). Wet granulation, dry granulation or dry blending may be used. In one wet granulation aspect, powdered ingredients are first mixed together and then mixed with a solution or suspension of the polymer (e.g., PVP). The resulting composition can be dried, granulated, mixed with lubricant and compressed to tablet form using conventional equipment. An example of an aerosol formulation can be prepared by dissolving the compound, for example 5-400 mg, of the disclosure in a suitable buffer solution, e.g. a phosphate buffer, adding a tonicifier, e.g. a salt such sodium chloride, if desired. The solution may be filtered, e.g., using a 0.2 micron filter, to remove impurities and contaminants. [0249] For treatment of the eye or other external tissues, e.g., mouth and skin, the formulations are preferably applied as a topical ointment or cream containing the compounds of the disclosure in an amount of, for example, 0.075 to 20% w/w. When formulated in an ointment, the compounds of the disclosure can be employed with either a paraffinic or a water-miscible ointment base. Alternatively, the compounds of the disclosure can be formulated in a cream with an oil-in-water cream base. If desired, the aqueous phase of the cream base can include a polyhydric alcohol, i.e., an alcohol having two or more hydroxyl groups such as propylene glycol, butane 1,3-diol, mannitol, sorbitol, glycerol and polyethylene glycol (including PEG 400) and mixtures thereof. The topical formulations can desirably include a compound which enhances absorption or penetration of a compound of the disclosure through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethyl sulfoxide and related analogs. [0250] For topical formulations, it is desired to administer an effective amount of a pharmaceutical composition according to the disclosure to target area, e.g., skin surfaces, mucous membranes, and the like, which are adjacent to peripheral neurons which are to be treated. This amount will generally range from about 0.0001 mg to about 1 g of a compound of the disclosure (or an embodiment or aspect thereof) per application, depending upon the area to be treated, whether the use is diagnostic, prophylactic or therapeutic, the severity of the symptoms, and the nature of the topical vehicle employed. A preferred topical preparation is an ointment, wherein about 0.001 to about 50 mg of a compound of the disclosure is used per cc of ointment base. The pharmaceutical composition can be formulated as transdermal compositions or transdermal delivery devices (“patches”). Such compositions include, for example, a backing, compound of the disclosure reservoir, a control membrane, liner and contact adhesive. Such transdermal patches may be used to provide continuous pulsatile, or on demand delivery of the compounds of the present disclosure as desired. [0251] The formulations can be packaged in unit-dose or multi-dose containers, for example sealed ampoules and vials, and can be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water, for injection immediately prior to use. Extemporaneous injection solutions and suspensions are prepared from sterile powders, granules and tablets of the kind previously described. Preferred unit dosage formulations are those containing a daily dose or unit daily sub-dose, as herein above recited, or an appropriate fraction thereof, of a compound of the disclosure. [0252] When the binding target is located in the brain, certain aspects of the disclosure provide for a compound of the disclosure (or an embodiment or aspect thereof) to traverse the blood-brain barrier. Certain neurodegenerative diseases are associated with an increase in permeability of the blood-brain barrier, such that a compound of the disclosure (or an embodiment or aspect thereof) can be readily introduced to the brain. When the blood-brain barrier remains intact, several art-known approaches exist for transporting molecules across it, including, but not limited to, physical methods, lipid-based methods, and receptor and channel-based methods. [0253] Physical methods of transporting a compound of the disclosure (or an embodiment or aspect thereof) across the blood-brain barrier include, but are not limited to, circumventing the blood- brain barrier entirely, or by creating openings in the blood-brain barrier. [0254] Circumvention methods include, but are not limited to, direct injection into the brain (see, e.g., Papanastassiou et al., Gene Therapy 9:398-406, 2002), interstitial infusion/convection-enhanced delivery (see, e.g., Bobo et al., Proc. Natl. Acad. Sci. U.S.A. 91 :2076-2080, 1994), and implanting a delivery device in the brain (see, e.g., Gill et al., Nature Med. 9:589-595, 2003; and Gliadel Wafers™, Guildford Pharmaceutical). [0255] Methods of creating openings in the barrier include, but are not limited to, ultrasound (see, e.g., U.S. Patent Publication No. 2002/0038086), osmotic pressure (e.g., by administration of hypertonic mannitol (Neuwelt, E. A., Implication of the Blood-Brain Barrier and its Manipulation, Volumes 1 and 2, Plenum Press, N.Y., 1989)), and permeabilization by, e.g., bradykinin or permeabilizer A-7 (see, e.g., U.S. Patent Nos.5,112,596, 5,268,164, 5,506,206, and 5,686,416). [0256] Lipid-based methods of transporting a compound of formula of the disclosure (or an embodiment or aspect thereof) across the blood-brain barrier include, but are not limited to, encapsulating the a compound of the disclosure (or an embodiment or aspect thereof) in liposomes that are coupled to antibody binding fragments that bind to receptors on the vascular endothelium of the blood- brain barrier (see, e.g., U.S. Patent Application Publication No.2002/0025313), and coating a compound of the disclosure (or an embodiment or aspect thereof) in low-density lipoprotein particles (see, e.g., U.S. Patent Application Publication No. 2004/0204354) or apolipoprotein E (see, e.g., U.S. Patent Application Publication No.2004/0131692). [0257] Receptor and channel-based methods of transporting a compound of the disclosure (or an embodiment or aspect thereof) across the blood-brain barrier include, but are not limited to, using glucocorticoid blockers to increase permeability of the blood-brain barrier (see, e.g., U.S. Patent Application Publication Nos.2002/0065259, 2003/0162695, and 2005/0124533); activating potassium channels (see, e.g., U.S. Patent Application Publication No.2005/0089473), inhibiting ABC drug transporters (see, e.g., U.S. Patent Application Publication No.2003/0073713); coating a compound of the disclosure (or an embodiment or aspect thereof) with a transferrin and modulating activity of the one or more transferrin receptors (see, e.g., U.S. Patent Application Publication No. 2003/0129186), and cationizing the antibodies (see, e.g., U.S. Patent No. 5,004,697). [0258] For intracerebral use, in certain aspects, the compounds can be administered continuously by infusion into the fluid reservoirs of the CNS, although bolus injection may be acceptable. The inhibitors can be administered into the ventricles of the brain or otherwise introduced into the CNS or spinal fluid. Administration can be performed by use of an indwelling catheter and a continuous administration means such as a pump, or it can be administered by implantation, e.g., intracerebral implantation of a sustained-release vehicle. More specifically, the inhibitors can be injected through chronically implanted cannulas or chronically infused with the help of osmotic mini pumps. Subcutaneous pumps are available that deliver proteins through a small tubing to the cerebral ventricles. Highly sophisticated pumps can be refilled through the skin and their delivery rate can be set without surgical intervention. Examples of suitable administration protocols and delivery systems involving a subcutaneous pump device or continuous intracerebroventricular infusion through a totally implanted drug delivery system are those used for the administration of dopamine, dopamine agonists, and cholinergic agonists to Alzheimer's disease patients and animal models for Parkinson's disease, as described by Harbaugh, J. Neural Transm. Suppl.24:271, 1987; and DeYebenes et al., Mov. Disord.2: 143, 1987. INDICATIONS AND METHODS OF TREATMENT [0259] Representative compounds of the disclosure have been shown to modulate TEAD activity. In some embodiments, a compound that modulates TEAD activity is a compound of formula (C-1), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: X1 is N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH ₂ , N(R ^e )(R ^f ), C _3-10 cycloalkyl, C _1-6 alkoxy, C _6-20 aryl, and C _1-6 alkyl, wherein the C _1-6 alkyl of R ₅ is optionally substituted with hydroxyl or N(R ^e )(R ^f ), or the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl; X ₂ and X ₃ are each independently N or C-R ₅ , wherein each R ₅ is independently selected from the group consisting of H, cyano, halo, C(O)NH ₂ , N(R ^e )(R ^f ), C _3-10 cycloalkyl, C _1-6 alkoxy, C _6-20 aryl, and C1-6alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ); X ₃ is N or C-H, R1 is: (i) oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more -C(O)NH2, or (ii) N(R ^e )(CN), or R _{a (iii)} ^Rc , wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, or (iv) , wherein R _d is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C1- 6alkyl is further optionally substituted with hydroxyl; L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; R2 is C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- 13spirocyclyl, or 5-20 membered heteroaryl, wherein the C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- ₁₃ spirocyclyl, or 5-20 membered heteroaryl of R ₂ is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1- 6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), O(R ^e ), and SF5; R ₃ is cyano, C _1-6 alkyl, C _1-4 alkoxy, or C _2-4 alkenyl, wherein the C _2-4 alkenyl is optionally substituted with N(R ^e )(R ^f ), or R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH, or R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl; R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl; and R ^e and R ^f are, independently of each other and independently at each occurrence, selected from the group consisting of H, cyano, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl of R ^e and R ^f are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. [0260] In some embodiments, a compound that modulates TEAD activity is a compound of formula (C), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: X1 is N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C _1-6 alkyl of R ₅ is optionally substituted with hydroxyl or N(R ^e )(R ^f ), or the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl; X2 and X3 are each independently N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH ₂ , N(R ^e )(R ^f ), C _3-10 cycloalkyl, C _1-6 alkoxy, C _6-20 aryl, and C1-6alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ); X ₃ is N or C-H, R1 is: (i) oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C1-6alkyl, or (ii) N(R ^e )(CN), or _(iii) ^Rc , wherein R _a , R _b , and R _c are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, or (iv) , wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C1- ₆ alkyl is further optionally substituted with hydroxyl; L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; R2 is C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- 13spirocyclyl, or 5-20 membered heteroaryl, wherein the C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, C _{5- 13} spirocyclyl, or 5-20 membered heteroaryl of R ₂ is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- ₆ haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ); R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), or R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl, provided that X ₃ is CH, or R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl; R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl; and R ^e and R ^f are, independently of each other and independently at each occurrence, selected from the group consisting of H, cyano, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl of R ^e and R ^f are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, oxo, cyano, halo, NO ₂ , and hydroxyl. [0261] In some embodiments, a compound that modulates TEAD activity is a compound of formula (A), or a pharmaceutically acceptable salt thereof: X ₁ , X ₂ , and X ₃ are each independently N or C-R ₅ , wherein each R ₅ is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, or C1-6alkyl is optionally substituted; , wherein Ra, Rb, Rc, and Rd are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl is independently optionally substituted; L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; R2 is C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5-13spirocyclyl, or 5-20 membered heteroaryl, wherein the C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, C _5-13 spirocyclyl, or 5-20 membered heteroaryl is independently optionally substituted; R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C1-6alkyl, C1-4alkoxy, or C2-4alkenyl is independently optionally substituted; or R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl; or R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl; and R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted. [0262] In some embodiments, a compound that modulates TEAD activity is a compound of formula (B-1), formula (B), or formula (I) as defined above, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. In other embodiments, a compound that modulates TEAD activity is a compound of formula (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), as defined above, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0263] The compounds of the disclosure (or an embodiment or aspect thereof) are useful as a medical therapy for treating diseases and conditions mediated by TEAD activity. Such diseases and conditions include but are not limited to cancers including acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom's macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. [0264] In a specific embodiment, compounds of the disclosure (or an embodiment or aspect thereof) can be administered as a medical therapy to treat proliferative disorders including acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. [0265] In one specific aspect, compounds of the disclosure (or an embodiment or aspect thereof) are administered as a medical therapy to treat acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. [0266] In another aspect, the disclosure provides for a method for treating acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor, comprising the step of administering a therapeutically effective amount of a compound according to formulae (A), (B), (B-1), (C), (C-1), or (I) (or an embodiment or aspect thereof) as described elsewhere herein to a subject in need thereof. [0267] In another aspect, the disclosure provides for a compound of formulae (A), (B), (B- 1), (C), (C-1), or (I) as described elsewhere herein or (or an embodiment or aspect thereof) for modulating TEAD activity. In some embodiments, the disclosure provides for a pharmaceutically acceptable salt of compound of formulae (A), (B), (B-1), (C), (C-1) or (I) for modulating TEAD activity. [0268] In another aspect, the disclosure provides for a compound of formulae (A), (B), (B- 1), (C), (C-1), or (I) as described elsewhere herein, or an embodiment or aspect thereof such as a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof for use in medical therapy. [0269] In another aspect, the disclosure provides for a method for treatment or prophylaxis of acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor, comprising the step of administering a therapeutically effective amount of a compound according to formulae (A), (B), (B-1), (C), (C-1), or (I) (or an embodiment or aspect thereof) as described elsewhere herein to a subject in need thereof. [0270] In another aspect, the disclosure provides for a compound of formulae (A), (B), (B- 1), (C), (C-1), or (I) as described elsewhere herein or an embodiment or aspect thereof such as a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof for use in the treatment or prophylaxis of acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. [0271] In another aspect, the disclosure provides for the use of a compound of formulae (A), (B), (B-1), (C), (C-1), or (I) as described elsewhere herein or an embodiment or aspect thereof such as a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment or prophylaxis of acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. [0272] In another aspect, the disclosure provides for the use of a compound of formulae (A), (B), (B-1), (C), (C-1), or (I) as described elsewhere herein or an embodiment or aspect thereof such as a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof for the treatment or prophylaxis of acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor [0273] In another aspect, the disclosure provides for a method for treating acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor in a mammal (e.g., a human) comprising administering a compound of formulae (A), (B), (B-1), (C), (C-1), or (I) as described elsewhere herein or an embodiment or aspect thereof such as a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof to the mammal. [0274] In another aspect, the disclosure provides for a method for modulating TEAD activity, comprising contacting TEAD with a compound of formulae (A), (B), (B-1), (C), (C-1), or (I) as described elsewhere herein or an embodiment or aspect thereof such as a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. [0275] In another aspect, the disclosure provides for a compound of formulae (A), (B), (B- 1), (C), (C-1), or (I) as described elsewhere herein or an embodiment or aspect thereof such as a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof for the treatment or prophylaxis of a disease or condition mediated by TEAD activity. Within aspects of this embodiment, the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. [0276] In another aspect, the disclosure provides for the use of a compound of formulae (A), (B), (B-1), (C), (C-1), or (I) as described elsewhere herein or an embodiment or aspect thereof such as a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment or prophylaxis of a disease or condition that is mediated by TEAD activity. Within aspects of this embodiment, the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. [0277] In one aspect, compounds of the disclosure demonstrate higher potency as compared to other analogues. COMBINATION THERAPY [0278] The compounds of formula (A), (B), (B-1), (C), (C-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or salts thereof, may be employed alone or in combination with other agents for treatment. For example, the second agent of the pharmaceutical combination formulation or dosing regimen may have complementary activities to the compound of formula (A), (B), (B-1), (C), (C-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL) such that they do not adversely affect each other. The compounds may be administered together in a unitary pharmaceutical composition or separately. In one embodiment a compound or a pharmaceutically acceptable salt can be co-administered with a cytotoxic agent to treat proliferative diseases and cancer. [0279] The term “co-administering” refers to either simultaneous administration, or any manner of separate sequential administration, of a compound of formula (A), (B), (B-1), (C), (C- 1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or a salt thereof, and a further active pharmaceutical ingredient or ingredients, including cytotoxic agents and radiation treatment. If the administration is not simultaneous, the compounds are administered in a close time proximity to each other. Furthermore, it does not matter if the compounds are administered in the same dosage form, e.g. one compound may be administered topically and another compound may be administered orally. [0280] Those additional agents may be administered separately from an inventive compound-containing composition, as part of a multiple dosage regimen. Alternatively, those agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as part of a multiple dosage regime, the two active agents may be submitted simultaneously, sequentially or within a period of time from one another normally within five hours from one another. [0281] As used herein, the term “combination,” “combined,” and related terms refers to the simultaneous or sequential administration of therapeutic agents in accordance with this invention. For example, a compound of the present invention may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a single unit dosage form. Accordingly, the present invention provides a single unit dosage form comprising a compound of formula I or formula II, an additional therapeutic agent, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. [0282] The amount of both an inventive compound and additional therapeutic agent (in those compositions which comprise an additional therapeutic agent as described above) that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. In certain embodiments, compositions of this invention are formulated such that a dosage of between 0.01 - 100 mg/kg body weight/day of an inventive can be administered. [0283] Typically, any agent that has activity against a disease or condition being treated may be co-administered. Examples of such agents can be found in Cancer Principles and Practice of Oncology by V.T. Devita and S. Hellman (editors), 6 ^th edition (February 15, 2001), Lippincott Williams & Wilkins Publishers. A person of ordinary skill in the art would be able to discern which combinations of agents would be useful based on the particular characteristics of the drugs and the disease involved. [0284] In one embodiment, the treatment method includes the co-administration of a compound of formula (A), (B), (B-1), (C), (C-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and at least one cytotoxic agent. The term “cytotoxic agent” as used herein refers to a substance that inhibits or prevents a cellular function and/or causes cell death or destruction. Cytotoxic agents include, but are not limited to, radioactive isotopes (e.g., At ²¹¹ , I ¹³¹ , I ¹²⁵ , Y ⁹⁰ , Re ¹⁸⁶ , Re ¹⁸⁸ , Sm ¹⁵³ , Bi ²¹² , P ³² , Pb ²¹² and radioactive isotopes of Lu); chemotherapeutic agents; growth inhibitory agents; enzymes and fragments thereof such as nucleolytic enzymes; and toxins such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and/or variants thereof. [0285] Exemplary cytotoxic agents can be selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormonal analogues, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, immunotherapeutic agents, proapoptotic agents, inhibitors of LDH-A; inhibitors of fatty acid biosynthesis; cell cycle signaling inhibitors; HDAC inhibitors, proteasome inhibitors; and inhibitors of cancer metabolism. [0286] “Chemotherapeutic agent” includes chemical compounds useful in the treatment of cancer. Examples of chemotherapeutic agents include erlotinib (TARCEVA ^® , Genentech/OSI Pharm.), bortezomib (VELCADE ^® , Millennium Pharm.), disulfiram , epigallocatechin gallate , salinosporamide A, carfilzomib, 17-AAG(geldanamycin), radicicol, lactate dehydrogenase A (LDH-A), fulvestrant (FASLODEX ^® , AstraZeneca), sunitib (SUTENT ^® , Pfizer/Sugen), letrozole (FEMARA ^® , Novartis), imatinib mesylate (GLEEVEC ^® ., Novartis), finasunate (VATALANIB ^® , Novartis), oxaliplatin (ELOXATIN ^® , Sanofi), 5-FU (5-fluorouracil), leucovorin, Rapamycin (Sirolimus, RAPAMUNE ^® , Wyeth), Lapatinib (TYKERB ^® , GSK572016, Glaxo Smith Kline), Lonafamib (SCH 66336), sorafenib (NEXAVAR ^® , Bayer Labs), gefitinib (IRESSA ^® , AstraZeneca), AG1478, alkylating agents such as thiotepa and CYTOXAN ^® cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including topotecan and irinotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogs); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); adrenocorticosteroids (including prednisone and prednisolone); cyproterone acetate; 5 ^-reductases including finasteride and dutasteride); vorinostat, romidepsin, panobinostat, valproic acid, mocetinostat dolastatin; aldesleukin, talc duocarmycin (including the synthetic analogs, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlomaphazine, chlorophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosoureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g., calicheamicin, especially calicheamicin γ1I and calicheamicin ω1I (Angew Chem. Intl. Ed. Engl. 1994 33:183-186); dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADRIAMYCIN ^® (doxorubicin), morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2- pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, porfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfomithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidamnol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2- ethylhydrazide; procarbazine; PSK ^® polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2''- trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids, e.g., TAXOL (paclitaxel; Bristol-Myers Squibb Oncology, Princeton, N.J.), ABRAXANE ^® (Cremophor-free), albumin-engineered nanoparticle formulations of paclitaxel (American Pharmaceutical Partners, Schaumberg, Ill.), and TAXOTERE ^® (docetaxel, doxetaxel; Sanofi- Aventis); chloranmbucil; GEMZAR ^® (gemcitabine); 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE ^® (vinorelbine); novantrone; teniposide; edatrexate; daunomycin; aminopterin; capecitabine (XELODA ^® ); ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; and pharmaceutically acceptable salts, acids and derivatives of any of the above. [0287] Chemotherapeutic agent also includes (i) anti-hormonal agents that act to regulate or inhibit hormone action on tumors such as anti-estrogens and selective estrogen receptor modulators (SERMs), including, for example, tamoxifen (including NOLVADEX ^® ; tamoxifen citrate), raloxifene, droloxifene, iodoxyfene , 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, and FARESTON ^® (toremifine citrate); (ii) aromatase inhibitors that inhibit the enzyme aromatase, which regulates estrogen production in the adrenal glands, such as, for example, 4(5)-imidazoles, aminoglutethimide, MEGASE ^® (megestrol acetate), AROMASIN ^® (exemestane; Pfizer), formestanie, fadrozole, RIVISOR ^® (vorozole), FEMARA ^® (letrozole; Novartis), and ARIMIDEX ^® (anastrozole; AstraZeneca); (iii) anti-androgens such as flutamide, nilutamide, bicalutamide, leuprolide and goserelin; buserelin, tripterelin, medroxyprogesterone acetate, diethylstilbestrol, premarin, fluoxymesterone, all transretionic acid, fenretinide, as well as troxacitabine (a 1,3-dioxolane nucleoside cytosine analog); (iv) protein kinase inhibitors; (v) lipid kinase inhibitors; (vi) antisense oligonucleotides, particularly those which inhibit expression of genes in signaling pathways implicated in aberrant cell proliferation, such as, for example, PKC- alpha, Ralf and H-Ras; (vii) ribozymes such as VEGF expression inhibitors (e.g., ANGIOZYME ^® ) and HER2 expression inhibitors; (viii) vaccines such as gene therapy vaccines, for example, ALLOVECTIN ^® , LEUVECTIN ^® , and VAXID ^® ; PROLEUKIN ^® , rIL-2; a topoisomerase 1 inhibitor such as LURTOTECAN ^® ; ABARELIX ^® rmRH; and (ix) pharmaceutically acceptable salts, acids and derivatives of any of the above. [0288] Chemotherapeutic agent also includes antibodies such as alemtuzumab (Campath), bevacizumab (AVASTIN®, Genentech); cetuximab (ERBITUX®, Imclone); panitumumab (VECTIBIX®, Amgen), rituximab (RITUXAN®, Genentech/Biogen Idec), pertuzumab (OMNITARG®, 2C4, Genentech), trastuzumab (HERCEPTIN®, Genentech), tositumomab (Bexxar, Corixia), and the antibody drug conjugate, gemtuzumab ozogamicin (MYLOTARG®, Wyeth). Additional humanized monoclonal antibodies with therapeutic potential as agents in combination with the compounds of the invention include: apolizumab, aselizumab, atlizumab, bapineuzumab, bivatuzumab mertansine, cantuzumab mertansine, cedelizumab, certolizumab pegol, cidfusituzumab, cidtuzumab, daclizumab, eculizumab, efalizumab, epratuzumab, erlizumab, felvizumab, fontolizumab, gemtuzumab ozogamicin, inotuzumab ozogamicin, ipilimumab, labetuzumab, lintuzumab, matuzumab, mepolizumab, motavizumab, motovizumab, natalizumab, nimotuzumab, nolovizumab, numavizumab, ocrelizumab, omalizumab, palivizumab, pascolizumab, pecfusituzumab, pectuzumab, pexelizumab, ralivizumab, ranibizumab, reslivizumab, reslizumab, resyvizumab, rovelizumab, ruplizumab, sibrotuzumab, siplizumab, sontuzumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tefibazumab, tocilizumab, toralizumab, tucotuzumab celmoleukin, tucusituzumab, umavizumab, urtoxazumab, ustekinumab, visilizumab, and the anti–interleukin-12 (ABT-874/J695, Wyeth Research and Abbott Laboratories) which is a recombinant exclusively human-sequence, full-length IgG1 λ antibody genetically modified to recognize interleukin-12 p40 protein. [0289] Chemotherapeutic agent also includes “EGFR inhibitors,” which refers to compounds that bind to or otherwise interact directly with EGFR and prevent or reduce its signaling activity, and is alternatively referred to as an “EGFR antagonist.” Examples of such agents include antibodies and small molecules that bind to EGFR. Examples of antibodies which bind to EGFR include MAb 579 (ATCC CRL HB 8506), MAb 455 (ATCC CRL HB8507), MAb 225 (ATCC CRL 8508), MAb 528 (ATCC CRL 8509) (see, US Patent No. 4,943, 533, Mendelsohn et al.) and variants thereof, such as chimerized 225 (C225 or Cetuximab; ERBUTIX ^{^} ) and reshaped human 225 (H225) (see, WO 96/40210, Imclone Systems Inc.); IMC-11F8, a fully human, EGFR-targeted antibody (Imclone); antibodies that bind type II mutant EGFR (US Patent No.5,212,290); humanized and chimeric antibodies that bind EGFR as described in US Patent No. 5,891,996; and human antibodies that bind EGFR, such as ABX-EGF or Panitumumab (see WO98/50433, Abgenix/Amgen); EMD 55900 (Stragliotto et al. Eur. J. Cancer 32A:636-640 (1996)); EMD7200 (matuzumab) a humanized EGFR antibody directed against EGFR that competes with both EGF and TGF-alpha for EGFR binding (EMD/Merck); human EGFR antibody, HuMax-EGFR (GenMab); fully human antibodies known as E1.1, E2.4, E2.5, E6.2, E6.4, E2.11, E6. 3 and E7.6. 3 and described in US 6,235,883; MDX-447 (Medarex Inc.); and mAb 806 or humanized mAb 806 (Johns et al., J. Biol. Chem.279(29):30375-30384 (2004)). The anti-EGFR antibody may be conjugated with a cytotoxic agent, thus generating an immunoconjugate (see, e.g., EP659,439A2, Merck Patent GmbH). EGFR antagonists include small molecules such as compounds described in US Patent Nos: 5,616,582, 5,457,105, 5,475,001, 5,654,307, 5,679,683, 6,084,095, 6,265,410, 6,455,534, 6,521,620, 6,596,726, 6,713,484, 5,770,599, 6,140,332, 5,866,572, 6,399,602, 6,344,459, 6,602,863, 6,391,874, 6,344,455, 5,760,041, 6,002,008, and 5,747,498, as well as the following PCT publications: WO98/14451, WO98/50038, WO99/09016, and WO99/24037. Particular small molecule EGFR antagonists include OSI-774 (CP-358774, erlotinib, TARCEVA ^{^} Genentech/OSI Pharmaceuticals); PD 183805 (CI 1033, 2-propenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(4- morpholinyl)propoxy]-6-quinazolinyl]-, dihydrochloride, Pfizer Inc.); ZD1839, gefitinib (IRESSA®) 4-(3’-Chloro-4’-fluoroanilino)-7-methoxy-6-(3-morpholino propoxy)quinazoline, AstraZeneca); ZM 105180 ((6-amino-4-(3-methylphenyl-amino)-quinazoline, Zeneca); BIBX- 1382 (N8-(3-chloro-4-fluoro-phenyl)-N2-(1-methyl-piperidin-4-yl)- pyrimido[5,4-d]pyrimidine- 2,8-diamine, Boehringer Ingelheim); PKI-166 ((R)-4-[4-[(1-phenylethyl)amino]-1H-pyrrolo[2,3- d]pyrimidin-6-yl]-phenol); (R)-6-(4-hydroxyphenyl)-4-[(1-phenylethyl)amino]-7H-pyrrolo[ 2,3- d]pyrimidine); CL-387785 (N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-butynamide); EKB- 569 (N-[4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxy-6-qu inolinyl]-4- (dimethylamino)-2-butenamide) (Wyeth); AG1478 (Pfizer); AG1571 (SU 5271; Pfizer); dual EGFR/HER2 tyrosine kinase inhibitors such as lapatinib (TYKERB®, GSK572016 or N-[3- chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6[5[[[2methylsulfo nyl)ethyl]amino]methyl]-2- furanyl]-4-quinazolinamine). [0290] Chemotherapeutic agents also include “tyrosine kinase inhibitors” including the EGFR-targeted drugs noted in the preceding paragraph; small molecule HER2 tyrosine kinase inhibitor such as TAK165 available from Takeda; CP-724,714, an oral selective inhibitor of the ErbB2 receptor tyrosine kinase (Pfizer and OSI); dual-HER inhibitors such as EKB-569 (available from Wyeth) which preferentially binds EGFR but inhibits both HER2 and EGFR-overexpressing cells; lapatinib (GSK572016; available from Glaxo-SmithKline), an oral HER2 and EGFR tyrosine kinase inhibitor; PKI-166 (available from Novartis); pan-HER inhibitors such as canertinib (CI-1033; Pharmacia); Raf-1 inhibitors such as antisense agent ISIS-5132 available from ISIS Pharmaceuticals which inhibit Raf-1 signaling; non-HER targeted TK inhibitors such as imatinib mesylate (GLEEVEC®, available from Glaxo SmithKline); multi-targeted tyrosine kinase inhibitors such as sunitinib (SUTENT®, available from Pfizer); VEGF receptor tyrosine kinase inhibitors such as vatalanib (PTK787/ZK222584, available from Novartis/Schering AG); MAPK extracellular regulated kinase I inhibitor CI-1040 (available from Pharmacia); quinazolines, such as PD 153035,4-(3-chloroanilino) quinazoline; pyridopyrimidines; pyrimidopyrimidines; pyrrolopyrimidines, such as CGP 59326, CGP 60261 and CGP 62706; pyrazolopyrimidines, 4-(phenylamino)-7H-pyrrolo[2,3-d] pyrimidines; curcumin (diferuloyl methane, 4,5-bis (4-fluoroanilino)phthalimide); tyrphostines containing nitrothiophene moieties; PD-0183805 (Warner-Lamber); antisense molecules (e.g. those that bind to HER-encoding nucleic acid); quinoxalines (US Patent No.5,804,396); tryphostins (US Patent No.5,804,396); ZD6474 (Astra Zeneca); PTK-787 (Novartis/Schering AG); pan-HER inhibitors such as CI-1033 (Pfizer); Affinitac (ISIS 3521; Isis/Lilly); imatinib mesylate (GLEEVEC®); PKI 166 (Novartis); GW2016 (Glaxo SmithKline); CI-1033 (Pfizer); EKB-569 (Wyeth); Semaxinib (Pfizer); ZD6474 (AstraZeneca); PTK-787 (Novartis/Schering AG); INC-1C11 (Imclone), rapamycin (sirolimus, RAPAMUNE®); or as described in any of the following patent publications: US Patent No. 5,804,396; WO 1999/09016 (American Cyanamid); WO 1998/43960 (American Cyanamid); WO 1997/38983 (Warner Lambert); WO 1999/06378 (Warner Lambert); WO 1999/06396 (Warner Lambert); WO 1996/30347 (Pfizer, Inc.); WO 1996/33978 (Zeneca); WO 1996/3397 (Zeneca) and WO 1996/33980 (Zeneca). [0291] Chemotherapeutic agents also include dexamethasone, interferons, colchicine, metoprine, cyclosporine, amphotericin, metronidazole, alemtuzumab, alitretinoin, allopurinol, amifostine, arsenic trioxide, asparaginase, BCG live, bevacuzimab, bexarotene, cladribine, clofarabine, darbepoetin alfa, denileukin, dexrazoxane, epoetin alfa, elotinib, filgrastim, histrelin acetate, ibritumomab, interferon alfa-2a, interferon alfa-2b, lenalidomide, levamisole, mesna, methoxsalen, nandrolone, nelarabine, nofetumomab, oprelvekin, palifermin, pamidronate, pegademase, pegaspargase, pegfilgrastim, pemetrexed disodium, plicamycin, porfimer sodium, quinacrine, rasburicase, sargramostim, temozolomide, VM-26, 6-TG, toremifene, tretinoin, ATRA, valrubicin, zoledronate, and zoledronic acid, and pharmaceutically acceptable salts thereof. [0292] Chemotherapeutic agents also include hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, triamcinolone acetonide, triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, fluocortolone, hydrocortisone-17-butyrate, hydrocortisone-17-valerate, aclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone- 17-butyrate, clobetasol-17-propionate, fluocortolone caproate, fluocortolone pivalate and fluprednidene acetate; immune selective anti-inflammatory peptides (ImSAIDs) such as phenylalanine-glutamine-glycine (FEG) and its D-isomeric form (feG) (IMULAN BioTherapeutics, LLC); anti-rheumatic drugs such as azathioprine, ciclosporin (cyclosporine A), D-penicillamine, gold salts, hydroxychloroquine, leflunomideminocycline, sulfasalazine, tumor necrosis factor alpha (TNFα) blockers such as etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi), Interleukin 1 (IL-1) blockers such as anakinra (Kineret), T cell costimulation blockers such as abatacept (Orencia), Interleukin 6 (IL-6) blockers such as tocilizumab (ACTEMERA®); Interleukin 13 (IL-13) blockers such as lebrikizumab; Interferon alpha (IFN) blockers such as Rontalizumab; Beta 7 integrin blockers such as rhuMAb Beta7; IgE pathway blockers such as Anti-M1 prime; Secreted homotrimeric LTa3 and membrane bound heterotrimer LTa1/β2 blockers such as Anti- lymphotoxin alpha (LTa); radioactive isotopes (e.g., At ²¹¹ , I ¹³¹ , I ¹²⁵ , Y ⁹⁰ , Re ¹⁸⁶ , Re ¹⁸⁸ , Sm ¹⁵³ , Bi ²¹² , P ³² , Pb ²¹² and radioactive isotopes of Lu); miscellaneous investigational agents such as thioplatin, PS-341, phenylbutyrate, ET-18- OCH3, or farnesyl transferase inhibitors (L-739749, L-744832); polyphenols such as quercetin, resveratrol, piceatannol, epigallocatechine gallate, theaflavins, flavanols, procyanidins, betulinic acid and derivatives thereof; autophagy inhibitors such as chloroquine; delta-9-tetrahydrocannabinol (dronabinol, MARINOL®); beta-lapachone; lapachol; colchicines; betulinic acid; acetylcamptothecin, scopolectin, and 9-aminocamptothecin); podophyllotoxin; tegafur (UFTORAL®); bexarotene (TARGRETIN®); bisphosphonates such as clodronate (for example, BONEFOS® or OSTAC®), etidronate (DIDROCAL®), NE-58095, zoledronic acid/zoledronate (ZOMETA®), alendronate (FOSAMAX®), pamidronate (AREDIA®), tiludronate (SKELID®), or risedronate (ACTONEL®); and epidermal growth factor receptor (EGF-R); vaccines such as THERATOPE® vaccine; perifosine, COX-2 inhibitor (e.g. celecoxib or etoricoxib), proteosome inhibitor (e.g. PS341); CCI-779; tipifarnib (R11577); orafenib, ABT510; Bcl-2 inhibitor such as oblimersen sodium (GENASENSE®); pixantrone; farnesyltransferase inhibitors such as lonafarnib (SCH 6636, SARASAR ^TM ); and pharmaceutically acceptable salts, acids or derivatives of any of the above; as well as combinations of two or more of the above such as CHOP, an abbreviation for a combined therapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone; and FOLFOX, an abbreviation for a treatment regimen with oxaliplatin (ELOXATIN ^TM ) combined with 5-FU and leucovorin. [0293] Chemotherapeutic agents also include non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory effects. NSAIDs include non-selective inhibitors of the enzyme cyclooxygenase. Specific examples of NSAIDs include aspirin, propionic acid derivatives such as ibuprofen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin and naproxen, acetic acid derivatives such as indomethacin, sulindac, etodolac, diclofenac, enolic acid derivatives such as piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam and isoxicam, fenamic acid derivatives such as mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, and COX-2 inhibitors such as celecoxib, etoricoxib, lumiracoxib, parecoxib, rofecoxib, rofecoxib, and valdecoxib. NSAIDs can be indicated for the symptomatic relief of conditions such as rheumatoid arthritis, osteoarthritis, inflammatory arthropathies, ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome, acute gout, dysmenorrhoea, metastatic bone pain, headache and migraine, postoperative pain, mild-to-moderate pain due to inflammation and tissue injury, pyrexia, ileus, and renal colic. [0294] In certain embodiments, chemotherapeutic agents include, but are not limited to, doxorubicin, dexamethasone, vincristine, cyclophosphamide, fluorouracil, topotecan, interferons, platinum derivatives, taxanes (e.g., paclitaxel, docetaxel), vinca alkaloids (e.g., vinblastine), anthracyclines (e.g., doxorubicin), epipodophyllotoxins (e.g., etoposide), cisplatin, an mTOR inhibitor (e.g., a rapamycin), methotrexate, actinomycin D, dolastatin 10, colchicine, trimetrexate, metoprine, cyclosporine, daunorubicin, teniposide, amphotericin, alkylating agents (e.g., chlorambucil), 5-fluorouracil, campthothecin, cisplatin, metronidazole, and imatinib mesylate, among others. In other embodiments, a compound of the present invention is administered in combination with a biologic agent, such as bevacizumab or panitumumab. [0295] In certain embodiments, compounds of the present invention, or a pharmaceutically acceptable composition thereof, are administered in combination with an antiproliferative or chemotherapeutic agent selected from any one or more of abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, amifostine, anastrozole, arsenic trioxide, asparaginase, azacitidine, BCG live, bevacuzimab, fluorouracil, bexarotene, bleomycin, bortezomib, busulfan, calusterone, capecitabine, camptothecin, carboplatin, carmustine, cetuximab, chlorambucil, cladribine, clofarabine, cyclophosphamide, cytarabine, dactinomycin, darbepoetin alfa, daunorubicin, denileukin, dexrazoxane, docetaxel, doxorubicin (neutral), doxorubicin hydrochloride, dromostanolone propionate, epirubicin, epoetin alfa, elotinib, estramustine, etoposide phosphate, etoposide, exemestane, filgrastim, floxuridine, fludarabine, fulvestrant, gefitinib, gemcitabine, gemtuzumab, goserelin acetate, histrelin acetate, hydroxyurea, ibritumomab, idarubicin, ifosfamide, imatinib mesylate, interferon alfa-2a, interferon alfa-2b, irinotecan, lenalidomide, letrozole, leucovorin, leuprolide acetate, levamisole, lomustine, megestrol acetate, melphalan, mercaptopurine, 6-MP, mesna, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone, nelarabine, nofetumomab, oprelvekin, oxaliplatin, paclitaxel, palifermin, pamidronate, pegademase, pegaspargase, pegfilgrastim, pemetrexed disodium, pentostatin, pipobroman, plicamycin, porfimer sodium, procarbazine, quinacrine, rasburicase, rituximab, sargramostim, sorafenib, streptozocin, sunitinib maleate, talc, tamoxifen, temozolomide, teniposide, VM-26, testolactone, thioguanine, 6-TG, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, tretinoin, ATRA, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, zoledronate, or zoledronic acid. [0296] Chemotherapeutic agents also include treatments for Alzheimer's Disease such as donepezil hydrochloride and rivastigmine; treatments for Parkinson's Disease such as L- DOPA/carbidopa, entacapone, ropinrole, pramipexole, bromocriptine, pergolide, trihexephendyl, and amantadine; agents for treating multiple sclerosis (MS) such as beta interferon (e.g., Avonex ^® and Rebif ^® ), glatiramer acetate, and mitoxantrone; treatments for asthma such as albuterol and montelukast sodium; agents for treating schizophrenia such as zyprexa, risperdal, seroquel, and haloperidol; anti-inflammatory agents such as corticosteroids, TNF blockers, IL-1 RA, azathioprine, cyclophosphamide, and sulfasalazine; immunomodulatory and immunosuppressive agents such as cyclosporin, tacrolimus, rapamycin, mycophenolate mofetil, interferons, corticosteroids, cyclophophamide, azathioprine, and sulfasalazine; neurotrophic factors such as acetylcholinesterase inhibitors, MAO inhibitors, interferons, anti-convulsants, ion channel blockers, riluzole, and anti-Parkinsonian agents; agents for treating cardiovascular disease such as beta-blockers, ACE inhibitors, diuretics, nitrates, calcium channel blockers, and statins; agents for treating liver disease such as corticosteroids, cholestyramine, interferons, and anti-viral agents; agents for treating blood disorders such as corticosteroids, anti-leukemic agents, and growth factors; and agents for treating immunodeficiency disorders such as gamma globulin. [0297] Additionally, chemotherapeutic agents include pharmaceutically acceptable salts, acids or derivatives of any of chemotherapeutic agents, described herein, as well as combinations of two or more of them. [0298] In another embodiment, provided are methods of using a compound of formula (A) (B), (B-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof as described elsewhere herein, or an embodiment or aspect thereof, to treat cancer in combination with a PD-1 axis binding antagonist. [0299] The term “PD-1 axis binding antagonist” refers to a molecule that inhibits the interaction of a PD-1 axis binding partner with either one or more of its binding partner, so as to remove T-cell dysfunction resulting from signaling on the PD-1 signaling axis – with a result being to restore or enhance T-cell function (e.g., proliferation, cytokine production, target cell killing). As used herein, a PD-1 axis binding antagonist includes a PD-1 binding antagonist, a PD-L1 binding antagonist and a PD-L2 binding antagonist. [0300] The term “PD-1 binding antagonist” refers to a molecule that decreases, blocks, inhibits, abrogates or interferes with signal transduction resulting from the interaction of PD-1 with one or more of its binding partners, such as PD-L1, PD-L2. In some embodiments, the PD- 1 binding antagonist is a molecule that inhibits the binding of PD-1 to one or more of its binding partners. In a specific aspect, the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1 and/or PD-L2. For example, PD-1 binding antagonists include anti-PD-1 antibodies, antigen binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-1 with PD-L1 and/or PD-L2. In one embodiment, a PD-1 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signaling through PD-1 so as render a dysfunctional T-cell less dysfunctional (e.g., enhancing effector responses to antigen recognition). In some embodiments, the PD-1 binding antagonist is an anti-PD-1 antibody. Specific examples of PD-1 binding antagonists are provided infra. [0301] The term “PD-L1 binding antagonist” refers to a molecule that decreases, blocks, inhibits, abrogates or interferes with signal transduction resulting from the interaction of PD-L1 with either one or more of its binding partners, such as PD-1, B7-1. In some embodiments, a PD- L1 binding antagonist is a molecule that inhibits the binding of PD-L1 to its binding partners. In a specific aspect, the PD-L1 binding antagonist inhibits binding of PD-L1 to PD-1 and/or B7-1. In some embodiments, the PD-L1 binding antagonists include anti-PD-L1 antibodies, antigen binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-L1 with one or more of its binding partners, such as PD-1, B7-1. In one embodiment, a PD-L1 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signaling through PD-L1 so as to render a dysfunctional T-cell less dysfunctional (e.g., enhancing effector responses to antigen recognition). In some embodiments, a PD-L1 binding antagonist is an anti-PD-L1 antibody. Specific examples of PD-L1 binding antagonists are provided infra. [0302] The term “PD-L2 binding antagonist” refers to a molecule that decreases, blocks, inhibits, abrogates or interferes with signal transduction resulting from the interaction of PD-L2 with either one or more of its binding partners, such as PD-1. In some embodiments, a PD-L2 binding antagonist is a molecule that inhibits the binding of PD-L2 to one or more of its binding partners. In a specific aspect, the PD-L2 binding antagonist inhibits binding of PD-L2 to PD-1. In some embodiments, the PD-L2 antagonists include anti-PD-L2 antibodies, antigen binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-L2 with either one or more of its binding partners, such as PD-1. In one embodiment, a PD- L2 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signaling through PD-L2 so as render a dysfunctional T-cell less dysfunctional (e.g., enhancing effector responses to antigen recognition). In some embodiments, a PD-L2 binding antagonist is an immunoadhesin. [0303] PD-1 Axis Binding Antagonists [0304] Provided herein are methods for treating cancer in an individual comprising administering to the individual an effective amount of a PD-1 axis binding antagonist and a compound of formula (A), (B), (B-1), (C), (C-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, as described elsewhere herein. Also provided herein are methods of enhancing immune function or response in an individual (e.g., an individual having cancer) comprising administering to the individual an effective amount of a PD-1 axis binding antagonist and a compound of formula (A), (B), (B-1), (C), (C-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, as described elsewhere herein. [0305] In such methods, the PD-1 axis binding antagonist includes a PD-1 binding antagonist, a PDL1 binding antagonist, and/or a PDL2 binding antagonist. Alternative names for “PD-1” include CD279 and SLEB2. Alternative names for “PDL1” include B7-H1, B7-4, CD274, and B7-H. Alternative names for “PDL2” include B7-DC, Btdc, and CD273. In some embodiments, PD-1, PDL1, and PDL2 are human PD-1, PDL1 and PDL2. [0306] In some embodiments, the PD-1 binding antagonist is a molecule that inhibits the binding of PD-1 to its ligand binding partner(s). In a specific aspect the PD-1 ligand binding partners are PDL1 and/or PDL2. In another embodiment, a PDL1 binding antagonist is a molecule that inhibits the binding of PDL1 to its binding partner(s). In a specific aspect, PDL1 binding partner(s) are PD-1 and/or B7-1. In another embodiment, the PDL2 binding antagonist is a molecule that inhibits the binding of PDL2 to its binding partner(s). In a specific aspect, a PDL2 binding partner is PD-1. The antagonist may be an antibody, an antigen binding fragment thereof, an immunoadhesin, a fusion protein, an oligopeptide or a small molecule. If the antagonist is an antibody, in some embodiments the antibody comprises a human constant region selected from the group consisting of IgG1, IgG2, IgG3 and IgG4 [0307] Anti-PD-1 Antibodies [0308] In some embodiments, the PD-1 binding antagonist is an anti-PD-1 antibody. A variety of anti-PDL1 antibodies can be utilized in the methods disclosed herein. In any of the embodiments herein, the PD-1 antibody can bind to a human PD-1 or a variant thereof. In some embodiments the anti-PD-1 antibody is a monoclonal antibody. In some embodiments, the anti- PD-1 antibody is an antibody fragment selected from the group consisting of Fab, Fab’, Fab’-SH, Fv, scFv, and (Fab’)2 fragments. In some embodiments, the anti-PD-1 antibody is a chimeric or humanized antibody. In other embodiments, the anti-PD-1 antibody is a human antibody. [0309] In some embodiments, the anti-PD-1 antibody is nivolumab (CAS Registry Number: 946414-94-4). Nivolumab (Bristol-Myers Squibb/Ono), also known as MDX-1106-04, MDX-1106, ONO-4538, BMS-936558, and OPDIVO®, is an anti-PD-1 antibody described in WO2006/121168. Nivolumab comprises a heavy chain and a light chain sequence, wherein: (a) the heavy chain comprises the amino acid sequence. QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIW Y DGSKRYYADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLV TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVD KSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO:1), and (b) the light chain comprises the amino acid sequence: EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRA T GIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQSSNWPRTFGQGTKVEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:2). [0310] In some embodiments, the anti-PD-1 antibody comprises the six HVR sequences from SEQ ID NO:1 and SEQ ID NO:2 (e.g., the three heavy chain HVRs from SEQ ID NO:1 and the three light chain HVRs from SEQ ID NO:2). In some embodiments, the anti-PD-1 antibody comprises the heavy chain variable domain from SEQ ID NO:1 and the light chain variable domain from SEQ ID NO:2. [0311] In some embodiments, the anti-PD-1 antibody is pembrolizumab (CAS Registry Number: 1374853-91-4). Pembrolizumab (Merck), also known as MK-3475, Merck 3475, lambrolizumab, SCH-900475, and KEYTRUDA® is an anti-PD-1 antibody described in WO2009/114335. Pembrolizumab comprises a heavy chain and a light chain sequence, wherein: (a) the heavy chain comprises the amino acid sequence: QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWMGG I NPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARRDYRFDMGFDY W GQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS GV HTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCP PCP APEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHN AKTK PREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK GQPR EPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGS FFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO:3), and (b) the light chain comprises the amino acid sequence: EIVLTQSPAT LSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLIYLA SYLES GVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTFGGGTKVEIKRTVA APSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ DSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:4). [0312] In some embodiments, the anti-PD-1 antibody comprises the six HVR sequences from SEQ ID NO:3 and SEQ ID NO:4 (e.g., the three heavy chain HVRs from SEQ ID NO:3 and the three light chain HVRs from SEQ ID NO:4). In some embodiments, the anti-PD-1 antibody comprises the heavy chain variable domain from SEQ ID NO:3 and the light chain variable domain from SEQ ID NO:4. [0313] In some embodiments, the anti-PD-1 antibody is MEDI-0680 (AMP-514; AstraZeneca). MEDI-0680 is a humanized IgG4 anti-PD-1 antibody. [0314] In some embodiments, the anti-PD-1 antibody is PDR001 (CAS Registry No. 1859072-53-9; Novartis). PDR001 is a humanized IgG4 anti-PD1 antibody that blocks the binding of PDL1 and PDL2 to PD-1. [0315] In some embodiments, the anti-PD-1 antibody is REGN2810 (Regeneron). REGN2810 is a human anti-PD1 antibody. [0316] In some embodiments, the anti-PD-1 antibody is BGB-108 (BeiGene). In some embodiments, the anti-PD-1 antibody is BGB-A317 (BeiGene). [0317] In some embodiments, the anti-PD-1 antibody is JS-001 (Shanghai Junshi). JS- 001 is a humanized anti-PD1 antibody. [0318] In some embodiments, the anti-PD-1 antibody is STI-A1110 (Sorrento). STI- A1110 is a human anti-PD1 antibody. [0319] In some embodiments, the anti-PD-1 antibody is INCSHR-1210 (Incyte). INCSHR-1210 is a human IgG4 anti-PD1 antibody. [0320] In some embodiments, the anti-PD-1 antibody is PF-06801591 (Pfizer). [0321] In some embodiments, the anti-PD-1 antibody is TSR-042 (also known as ANB011; Tesaro/AnaptysBio). [0322] In some embodiments, the anti-PD-1 antibody is AM0001 (ARMO Biosciences). [0323] In some embodiments, the anti-PD-1 antibody is ENUM 244C8 (Enumeral Biomedical Holdings). ENUM 244C8 is an anti-PD1 antibody that inhibits PD-1 function without blocking binding of PDL1 to PD-1. [0324] In some embodiments, the anti-PD-1 antibody is ENUM 388D4 (Enumeral Biomedical Holdings). ENUM 388D4 is an anti-PD1 antibody that competitively inhibits binding of PDL1 to PD-1. [0325] In some embodiments, the PD-1 antibody comprises the six HVR sequences (e.g., the three heavy chain HVRs and the three light chain HVRs) and/or the heavy chain variable domain and light chain variable domain from a PD-1 antibody described in WO2015/112800 (Applicant: Regeneron), WO2015/112805 (Applicant: Regeneron), WO2015/112900 (Applicant: Novartis), US20150210769 (Assigned to Novartis), WO2016/089873 (Applicant: Celgene), WO2015/035606 (Applicant: Beigene), WO2015/085847 (Applicants: Shanghai Hengrui Pharmaceutical/Jiangsu Hengrui Medicine), WO2014/206107 (Applicants: Shanghai Junshi Biosciences/Junmeng Biosciences), WO2012/145493 (Applicant: Amplimmune), US9205148 (Assigned to MedImmune), WO2015/119930 (Applicants: Pfizer/Merck), WO2015/119923 (Applicants: Pfizer/Merck), WO2016/032927 (Applicants: Pfizer/Merck), WO2014/179664 (Applicant: AnaptysBio), WO2016/106160 (Applicant: Enumeral), and WO2014/194302 (Applicant: Sorrento). [0326] Anti-PDL1 Antibodies [0327] In some embodiments, the PD-1 axis binding antagonist is an anti-PDL1 antibody. A variety of anti-PDL1 antibodies are contemplated and described herein. In any of the embodiments herein, the isolated anti-PDL1 antibody can bind to a human PDL1, for example a human PDL1 as shown in UniProtKB/Swiss-Prot Accession No.Q9NZQ7.1, or a variant thereof. In some embodiments, the anti-PDL1 antibody is capable of inhibiting binding between PDL1 and PD-1 and/or between PDL1 and B7-1. In some embodiments, the anti-PDL1 antibody is a monoclonal antibody. In some embodiments, the anti-PDL1 antibody is an antibody fragment selected from the group consisting of Fab, Fab’-SH, Fv, scFv, and (Fab’)2 fragments. In some embodiments, the anti-PDL1 antibody is a chimeric or humanized antibody. In some embodiments, the anti-PDL1 antibody is a human antibody. Examples of anti-PDL1 antibodies useful in the methods of this invention and methods of making them are described in PCT patent application WO 2010/077634 and US Patent No.8,217,149, both of which are incorporated herein. [0328] In some embodiments, the anti-PDL1 antibody is atezolizumab (CAS Registry Number: 1422185-06-5). Atezolizumab (Genentech), also known as MPDL3280A, is an anti- PDL1 antibody. [0329] Atezolizumab comprises: (a) an HVR-H1, HVR-H2, and HVR-H3 sequence of GFTFSDSWIH (SEQ ID NO:5), AWISPYGGSTYYADSVKG (SEQ ID NO:6) and RHWPGGFDY (SEQ ID NO:7), respectively, and (b) an HVR-L1, HVR-L2, and HVR-L3 sequence of RASQDVSTAVA (SEQ ID NO:8), SASFLYS (SEQ ID NO:9) and QQYLYHPAT (SEQ ID NO:10), respectively. [0330] Atezolizumab comprises a heavy chain and a light chain sequence, wherein: (a) the heavy chain variable region sequence comprises the amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPY GGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQG TLVTVSS (SEQ ID NO:11, and (b) the light chain variable region sequence comprises the amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIY SASF LYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKR (SEQ ID NO: 12). [0331] Atezolizumab comprises a heavy chain and a light chain sequence, wherein: (a) the heavy chain comprises the amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPY GGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQG TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:13), and (b) the light chain comprises the amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLY SGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKRTVAAPSV F IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:14). [0332] In some embodiments, the anti-PDL1 antibody is avelumab (CAS Registry Number: 1537032-82-8). Avelumab, also known as MSB0010718C, is a human monoclonal IgG1 anti-PDL1 antibody (Merck KGaA, Pfizer). Avelumab comprises a heavy chain and a light chain sequence, wherein: (a) the heavy chain comprises the amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYIMMWVRQAPGKGLEWVSSIYPS GGITFYADTVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIKLGTVTTVDYWGQ GTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHT FPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:15), and (b) the light chain comprises the amino acid sequence: QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSN RPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVFGTGTKVTVLGQPKA NPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO:16). [0333] In some embodiments, the anti-PDL1 antibody comprises the six HVR sequences from SEQ ID NO:15 and SEQ ID NO:16 (e.g., the three heavy chain HVRs from SEQ ID NO:15 and the three light chain HVRs from SEQ ID NO:16). In some embodiments, the anti-PDL1 antibody comprises the heavy chain variable domain from SEQ ID NO:15 and the light chain variable domain from SEQ ID NO:16. [0334] In some embodiments, the anti-PDL1 antibody is durvalumab (CAS Registry Number: 1428935-60-7). Durvalumab, also known as MEDI4736, is an Fc-optimized human monoclonal IgG1 kappa anti-PDL1 antibody (MedImmune, AstraZeneca) described in WO2011/066389 and US2013/034559. Durvalumab comprises a heavy chain and a light chain sequence, wherein: (a) the heavy chain comprises the amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMSWVRQAPGKGLEWVANIKQ DGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAREGGWFGELAFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQ PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:17), and (b) the light chain comprises the amino acid sequence: EIVLTQSPGTLSLSPGERATLSCRASQRVSSSYLAWYQQKPGQAPRLLIYDASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSLPWTFGQGTKVEIKRTVAAPSV F IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:18). [0335] In some embodiments, the anti-PDL1 antibody comprises the six HVR sequences from SEQ ID NO:17 and SEQ ID NO:18 (e.g., the three heavy chain HVRs from SEQ ID NO:17 and the three light chain HVRs from SEQ ID NO:18). In some embodiments, the anti-PDL1 antibody comprises the heavy chain variable domain from SEQ ID NO:17 and the light chain variable domain from SEQ ID NO:18. [0336] In some embodiments, the anti-PDL1 antibody is MDX-1105 (Bristol Myers Squibb). MDX-1105, also known as BMS-936559, is an anti-PDL1 antibody described in WO2007/005874. [0337] In some embodiments, the anti-PDL1 antibody is LY3300054 (Eli Lilly). [0338] In some embodiments, the anti-PDL1 antibody is STI-A1014 (Sorrento). STI- A1014 is a human anti-PDL1 antibody. [0339] In some embodiments, the anti-PDL1 antibody is KN035 (Suzhou Alphamab). KN035 is single-domain antibody (dAB) generated from a camel phage display library. [0340] In some embodiments, the anti-PDL1 antibody comprises a cleavable moiety or linker that, when cleaved (e.g., by a protease in the tumor microenvironment), activates an antibody antigen binding domain to allow it to bind its antigen, e.g., by removing a non-binding steric moiety. In some embodiments, the anti-PDL1 antibody is CX-072 (CytomX Therapeutics). [0341] In some embodiments, the PDL1 antibody comprises the six HVR sequences (e.g., the three heavy chain HVRs and the three light chain HVRs) and/or the heavy chain variable domain and light chain variable domain from a PDL1 antibody described in US20160108123 (Assigned to Novartis), WO2016/000619 (Applicant: Beigene), WO2012/145493 (Applicant: Amplimmune), US9205148 (Assigned to MedImmune), WO2013/181634 (Applicant: Sorrento), and WO2016/061142 (Applicant: Novartis). [0342] In a still further specific aspect, the PD-1 or PDL1 antibody has reduced or minimal effector function. In a still further specific aspect the minimal effector function results from an “effector-less Fc mutation” or aglycosylation mutation. In still a further embodiment, the effector- less Fc mutation is an N297A or D265A/N297A substitution in the constant region. In some embodiments, the isolated anti-PDL1 antibody is aglycosylated. Glycosylation of antibodies is typically either N-linked or O- linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain. Thus, the presence of either of these tripeptide sequences in a polypeptide creates a potential glycosylation site. O-linked glycosylation refers to the attachment of one of the sugars N-aceylgalactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5- hydroxyproline or 5-hydroxylysine may also be used. Removal of glycosylation sites form an antibody is conveniently accomplished by altering the amino acid sequence such that one of the above-described tripeptide sequences (for N-linked glycosylation sites) is removed. The alteration may be made by substitution of an asparagine, serine or threonine residue within the glycosylation site another amino acid residue (e.g., glycine, alanine or a conservative substitution). [0343] Other PD-1 Antagonists [0344] In some embodiments, the PD-1 binding antagonist is an immunoadhesin (e.g., an immunoadhesin comprising an extracellular or PD-1 binding portion of PDL1 or PDL2 fused to a constant region (e.g., an Fc region of an immunoglobulin sequence). In some embodiments, the PD-1 binding antagonist is AMP-224. AMP-224 (CAS Registry No. 1422184-00-6; GlaxoSmithKline/MedImmune), also known as B7-DCIg, is a PDL2-Fc fusion soluble receptor described in WO2010/027827 and WO2011/066342. [0345] In some embodiments, the PD-1 binding antagonist is a peptide or small molecule compound. In some embodiments, the PD-1 binding antagonist is AUNP-12 (PierreFabre/Aurigene). See, e.g., WO2012/168944, WO2015/036927, WO2015/044900, WO2015/033303, WO2013/144704, WO2013/132317, and WO2011/161699. [0346] In some embodiments, the PDL1 binding antagonist is a small molecule that inhibits PD-1. In some embodiments, the PDL1 binding antagonist is a small molecule that inhibits PDL1. In some embodiments, the PDL1 binding antagonist is a small molecule that inhibits PDL1 and VISTA. In some embodiments, the PDL1 binding antagonist is CA-170 (also known as AUPM-170). In some embodiments, the PDL1 binding antagonist is a small molecule that inhibits PDL1 and TIM3. In some embodiments, the small molecule is a compound described in WO2015/033301 and WO2015/033299. [0347] In some embodiments, the treatment method includes the co-administration of a compound of formula (A), (B), (B-1), (C), (C-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, and at least one mitogen-activated protein kinase (MAPK) inhibitor. In some embodiments, the treatment method includes the co-administration of a compound of formula (A), (B), (B-1), (C), (C-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, and at least one inhibitor of the RAS/MAPK pathway. In some embodiments, the treatment method includes the co-administration of a compound of formula (A), (B), (B-1), (C), (C-1), (I), (IA), (IB), (IC), (IC-1), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), or (IL), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, and at least one epidermal growth factor receptor (EGFR) inhibitor. In some embodiments, the inhibitor of the RAS/MAPK pathway is a KRAS inhibitor, a RAF inhibitor, such as a BRAF monomer or RAF dimer inhibitor, a MEK inhibitor, an ERK inhibitor, an EGFR inhibitor, or a MAPK inhibitor, or any combination thereof. In certain embodiments, the inhibitor of the RAS/MAPK pathway is an EGFR inhibitor or a MAPK inhibitor, or a combination thereof. Examples of EGFR inhibitors, MAPK inhibitors, and/or RAS/MAPK pathway inhibitors are disclosed in Moore, A.R., Rosenberg, S.C., McCormick, F. et al. RAS-targeted therapies: is the undruggable drugged?. Nat Rev Drug Discov (2020) incorporated herein by reference and include, but are not limited to: sotorasib (AMG 510 from Amgen), MRTX849 (from Mirati Therapeutics), JNJ-74699157/ARS- 3248 (from J&J Wellspring Biosciences), LY3499446 (from Eli Lilly), GDCBI 1701963 (from Boehringer Ingelheim), mRNA-5671 (from Moderna Therapeutics), G12D inhibitor (from Mirati Therapeutics), RAS(ON) inhibitors (from Revolution Medicines), BBP-454 (from BridgeBio Pharma), SP600125, PLX4032, GW5074, AZD6244, PD98059, simvastatin, alisertib, teriflunomide, NSC95397, PD325901, PD98059, lovastatin, sorafenib (NEXAVAR ^® , Bayer Labs), vermurafenib (ZELBORAF ^® , Hoffman La Roche Inc.), dabrafenib (TAFLINAR ^® , Novartis Pharmaceuticals Corportation), selumetinib (KOSELUGO™, AstraZeneca Pharmaceuticals LP), trametinib (MEKINIST ^® , Novartis Pharmaceuticals Corporation), ulixertinib, silimarin, sirolimus (RAPAMUNE ^® , PV Prism CV), lapatinib (TYKERB ^® /TYVERB ^® , GlaxoSmithKline), crizotinib (XALKORI ^® , PF Prism CV), taselisib (Roche), PF-0491502, PF502, enterolactone, PLX4720, PD0325901, PD184352, SC-514, alisterib (MLN8237), SB415286, PLX4720, obtaoclax (GX15- 070), pimasterib, venetoclax (ABT-199/VENCLEXTA ^® /VENCLYXTO ^® ), eprenetapopt (APR- 246), gemcitabine (GEMZAR ^® ), birinapant (TL32711), pexmetinib (ARRY-614), afuresertib, ralimetinib (LY2228820, Eli Lilly), cobimetinib (COTELLIC ^® , Exelixis/Genentech), prexasertib (LY2606368), erlotinib (TARCEVA ^® , OSI Pharmaceuticals), bevacizumab (AVASTIN ^® , Genentech), belvarafenib (Hanmi Pharm./Genentech, Inc.), and binimetinib (MEKTOVI ^® , Array Biopharma Inc.). [0348] As used herein “combination” refers to any mixture or permutation of one or more compounds of the disclosure (or an embodiment or aspect thereof) and one or more other compounds of the disclosure or one or more additional therapeutic agent. Unless the context makes clear otherwise, “combination” may include simultaneous or sequentially delivery of a compound of the invention with one or more therapeutic agents. Unless the context makes clear otherwise, “combination” may include dosage forms of a compound of the disclosure with another therapeutic agent. Unless the context makes clear otherwise, “combination” may include routes of administration of a compound of the disclosure with another therapeutic agent. Unless the context makes clear otherwise, “combination” may include formulations of a compound of the disclosure with another therapeutic agent. Dosage forms, routes of administration and pharmaceutical compositions include, but are not limited to, those described herein. ENUMERATED EMBODIMENTS [0349] The following enumerated embodiments are representative of some aspects of the invention. 1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: X1 and X2 are each independently N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH ₂ , N(R ^e )(R ^f ), C _3-10 cycloalkyl, C _1-6 alkoxy, C _6-20 aryl, and C _1-6 alkyl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl or N(R ^e )(R ^f ); X ₃ is N or CH, provided that, when X3 is N, at least one of X1 and X2 is N; R1 is , wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; or , wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; R2 is C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- ₁₃ spirocyclyl, or 5-20 membered heteroaryl, wherein the C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5-13spirocyclyl, or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl- C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl; provided that, when R2 is C1-12alkyl, wherein the C1-12alkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- ₆ haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), L is -CH=CH- or -C≡C-; R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), or R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, provided that X3 is CH, or R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl; provided that: (i) when R ₃ is cyano, C _1-6 alkyl, C _1-4 alkoxy, or C _2-4 alkenyl, wherein the C _2-4 alkenyl is optionally substituted with N(R ^e )(R ^f ), and R ₂ is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), L is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) when R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, provided that X3 is CH, and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), L is absent or is *-CH ₂ -O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (iii) when R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- ₆ haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), L is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; and R ₄ is H or C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl. 2. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein: X ₁ is C-R ₅ , wherein R ₅ is C _1-6 alkyl, C _1-6 alkoxy, or NH(R ^e ), and R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl, provided that X3 is CH. 3. The compound of embodiment 2, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (IA): or a pharmaceutically acceptable salt thereof. 4. The compound of embodiment 3, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (IA) is a compound selected from the group consisting of:

, or a pharmaceutically acceptable salt thereof. 5. The compound of embodiment 2, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (IB): or a pharmaceutically acceptable salt thereof. 6. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein: X1 is C-R5, wherein R5 is C1-6alkyl, C1-6alkoxy, or NH(R ^e ), and R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heteroaryl, provided that X ₃ is CH. 7. The compound of embodiment 6, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (IC): or a pharmaceutically acceptable salt thereof. 8. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein: L is *-CH2-O-**, and R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C ₆ aryl. 9. The compound of embodiment 8, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (ID): or a pharmaceutically acceptable salt thereof. 10. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein: L is *-CH2-O-**, and R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a 6-membered heteroaryl. 11. The compound of embodiment 10, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (IE): , or a pharmaceutically acceptable salt thereof. 12. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein: X ₃ is CH, L is -CH-CH-, R2 is C3-10cycloalkyl, wherein the C3-10cycloalkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), R ₃ is C _1-4 alkoxy, and R4 is H. 13. The compound of embodiment 12, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of the formula (IF): or a pharmaceutically acceptable salt thereof. 14. The compound of embodiment 13, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (IF) is a compound selected from the group consisting of: , acceptable salt thereof. 15. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein R ₁ is , wherein R _a , R _b , and R _c are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule. 16. The compound of embodiment 15, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (IG): or a pharmaceutically acceptable salt thereof. 17. The compound of embodiment 15 or 16, or a pharmaceutically acceptable salt thereof, wherein L is -CH=CH- and R ₂ is C _3-10 cycloalkyl, wherein the C _3-10 cycloalkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ). 18. The compound of embodiment 17, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (IH): or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2, and each R _x , if present, is independently selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ). 19. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein R ₂ is C _1-12 alkyl, wherein the C _1-12 alkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3- 10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), and L is -CH=CH- or -C≡C-. 20. The compound of embodiment 19, or a pharmaceutically acceptable salt thereof, wherein L is -CH=CH-. 21. The compound of embodiment 19, or a pharmaceutically acceptable salt thereof, wherein L is -C≡C-. 22. A compound selected from the group consisting of:

23. A pharmaceutical composition, comprising a compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. 24. A compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, for use in medical therapy. 25. A compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, for use in the treatment and/or prophylaxis of acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T- cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 26. A method for treating cancer in a mammal, comprising administering a compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, to the mammal. 27. A compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, for use in modulating TEAD activity. 28. A compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, for use in the treatment and/or prophylaxis of a disease or condition mediated by TEAD activity. 29. The compound for use of embodiment 28, wherein the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 30. The use of a compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of prophylaxis of a disease or condition that is mediated by TEAD activity. 31. The use of embodiment 30, wherein the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T- cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 32. A method for modulating TEAD activity, comprising contacting TEAD with a compound as described in any one of embodiments 1-22, or a salt thereof. 33. A method for treating a disease or condition mediated by TEAD activity in a mammal, comprising administering a compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, to the mammal. 34. The method of embodiment 33, wherein the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 35. Use of a compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, for modulating TEAD activity. 36. Use of a compound as described in any one of embodiments 1-22, or a pharmaceutically acceptable salt thereof, for the treatment and/or prophylaxis of a disease or condition mediated by TEAD activity. 37. The use of embodiment 36, wherein the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T- cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 38. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein: X ₁ and X ₂ are each independently N or C-R ₅ , wherein R ₅ is selected from the group consisting of hydrogen, cyano, halo, C(O)NH ₂ , NH(R ^e ), C _1-6 alkyl, C _3-10 cycloalkyl, C _1-6 alkoxy, and C6-20aryl, wherein the C1-6alkyl is optionally substituted with hydroxyl; X ₃ is N or CH, provided that, when X ₃ is N, at least one of X ₁ and X ₂ is N; R1 is , wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; or , wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, C _1-6 alkyl, C _6-20 aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule; R2 is C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, or C5- ₁₃ spirocyclyl, wherein the C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, or C5-13spirocyclyl is independently optionally substituted with one, two, three, or four substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), wherein each R ^e and R ^f is independently selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl- C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of C _1-6 alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl; R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with NH(R ^e ); or R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, provided that X3 is CH; or R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl; and R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl. 39. A compound prepared by the process of embodiment 38. 40. A compound of formula (B): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: X1 is N or C-R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C _1-6 alkyl of R ₅ is optionally substituted with hydroxyl or N(R ^e )(R ^f ), or the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl, provided that X ₃ is CH; X ₂ is N or C-R ₅ , wherein each R ₅ is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(R ^e )(R ^f ), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(R ^e )(R ^f ); X3 is N or C-H, provided that, when , then at least one of X1 and X ₂ is N; R1 is: (i) oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C1-6alkyl, and L is absent or is selected from the group consisting of -O-, *-CH2-O-**, *-O-CH2-**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) N(R ^e )(CN), and L is absent or is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or _(iii) wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5- 20 membered heteroaryl, wherein the C _1-6 alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH2-O-**, *-O-CH2-**, - CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (iv) wherein R _d is selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C1- 6alkyl is further optionally substituted with hydroxyl, and L is selected from the group consisting of -O-, *-CH ₂ -O-**, *-O-CH ₂ -**, -CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule; R ₂ is C _1-12 alkyl, C _3-10 cycloalkyl, 3-10 membered saturated heterocyclyl, C _6-20 aryl, C _5- 13spirocyclyl, or 5-20 membered heteroaryl, wherein the C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C6-20aryl, C5- ₁₃ spirocyclyl, or 5-20 membered heteroaryl of R ₂ is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1- 6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), provided that, when R ₂ is C _1-12 alkyl, wherein the C _1-12 alkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is -CH=CH- or -C≡C-; R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), or R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5- membered heteroaryl is optionally substituted with one or more C _1-6 alkyl, provided that X ₃ is CH, or R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl, provided that, when: (i) R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(R ^e )(R ^f ), and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule, or (ii) R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5- membered heterocyclyl or a 5-membered heteroaryl, provided that X ₃ is CH, and R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3- 10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1- 6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ), then L is absent or is *-CH2-O-**, -CH=CH-, or -C≡C-, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule, or (iii) R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a C ₆ aryl or a 6-membered heteroaryl, and , then R2 is 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl, wherein the 3-10 membered saturated heterocyclyl or 5-20 membered heteroaryl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ); R ₄ is H or C _1-6 alkyl, wherein the C _1-6 alkyl is optionally substituted with hydroxyl; and R ^e and R ^f are, independently of each other and independently at each occurrence, selected from the group consisting of H, cyano, hydroxyl, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _1-6 alkyl-C _3-10 cycloalkyl, 3-10 membered heterocyclyl, C _6-20 aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-20aryl, and 3-20 membered heteroaryl of R ^e and R ^f are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl. 41. The compound of embodiment 40, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: X1 is C-R5, wherein R5 is C1-6alkyl, C1-6alkoxy, or NH(R ^e ), and R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl, provided that X3 is CH. 42. The compound of embodiment 40 or embodiment 41, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B) is a compound of formula (IA):

or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 43. The compound of embodiment 42, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (IA) is a compound selected from the salt thereof. 44. The compound of embodiment 43, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is absent and R ₂ is C _6-20 aryl, wherein the C _6-20 aryl is optionally substituted with one or more C1-6alkyl. 45. The compound of embodiment 44, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X ₂ is C-R ₅ , wherein R ₅ is cyano. 46. The compound of embodiment 45, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (IA) is a compound of formula (IJ): or a stereosiomer, tautomer, or pharmaceutically acceptable salt thereof. 47. The compound of embodiment 46, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (IJ) is selected from the group

acceptable salt thereof. 48. The compound of embodiment 46, or a stereoisomer, tautomer, or pharamceutically acceptable salt thereof, wherein R ₁ is oxiranyl or oxetanyl, wherein the oxiranyl or oxetanyl is optionally substituted with one or more C1-6alkyl. 49. The compound of embodiment 48, or a stereoisomer, tautomer, or pharamceutically acceptable salt thereof, wherein the compound of formula (IJ) is a compound of formula (IK): wherein R _g is H or C _1-6 alkyl, or a stereosiomer, tautomer, or pharmaceutically acceptable salt thereof. 50. The compound of embodiment 46, or a stereoisomer, tautomer, or pharamceutically acceptable salt thereof, wherein R1 is N(R ^e )(CN). 51. The compound of embodiment 50, or a stereoisomer, tautomer, or pharamceutically acceptable salt thereof, wherein the compound of formula (IJ) is a compound of formula (IL):

or a stereosiomer, tautomer, or pharmaceutically acceptable salt thereof. 52. The compound of embodiment 51, or a stereoisomer, tautomer, or pharamceutically acceptable salt thereof, wherein R ^e is H or C _1-6 alkyl. 53. The compound of embodiment 41, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B) is a compound of formula (IB): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 54. The compound of embodiment 40, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: X ₁ is C-R ₅ , wherein R ₅ is C _1-6 alkyl, C _1-6 alkoxy, or NH(R ^e ), and R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C _1-6 alkyl, provided that X ₃ is CH. 55. The compound of embodiment 54, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B) is a compound of formula (IC):

or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 56. The compound of embodiment 40, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: L is *-CH2-O-**, and R ₃ is taken together with the carbon atom of *-CH ₂ -O-** of L, and the atoms to which they are attached, to form a C6aryl. 57. The compound of embodiment 56, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B) is a compound of formula (ID): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 58. The compound of embodiment 40, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: L is *-CH ₂ -O-**, and R3 is taken together with the carbon atom of *-CH2-O-** of L, and the atoms to which they are attached, to form a 6-membered heteroaryl. 59. The compound of embodiment 58, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B) is a compound of formula (IE): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 60. The compound of embodiment 40, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein: X3 is CH, L is -CH=CH-, R ₂ is C _3-10 cycloalkyl, wherein the C _3-10 cycloalkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), R ₃ is C _1-4 alkoxy, and R4 is H. 61. The compound of embodiment 60, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B) is a compound of the formula (IF): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 62. The compound of embodiment 61, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (IF) is a compound selected from the

stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 63. The compound of any one of embodiments 40-42, 44-46, and 53-61 or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein , wherein Ra, Rb, and R _c are each independently selected from the group consisting of H, halo, cyano, hydroxyl, C1-6alkyl, C6-20aryl, 3-10 membered heterocyclyl, and 5-20 membered heteroaryl, wherein the C1- 6alkyl is further optionally substituted with hydroxyl, provided that at least two of R ^a , R ^b , and R ^c are H, and L is absent or is selected from the group consisting of *-CH ₂ -O-**, *-O-CH ₂ -**, - CH=CH-, and -C≡C-, wherein ** indicates the attachment point to the R ₂ moiety and * indicates the attachment point to the remainder of the molecule. 64. The compound of embodiment 63, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B) is a compound of formula (IG): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 65. The compound of embodiment 64, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH- and R ₂ is C _3-10 cycloalkyl, wherein the C _3- 10cycloalkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ). 66. The compound of embodiment 65, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (B) is a compound of formula (IH): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2, and each R _x , if present, is independently selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(R ^e )(R ^f ), and O(R ^e ). 67. The compound of embodiment 66, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound of formula (IH) is selected from the group consisting of: ,

, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 68. The compound of embodiment 40, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R2 is C1-12alkyl, wherein the C1-12alkyl is independently optionally substituted with one or two substituents selected from the group consisting of cyano, halo, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, NO ₂ , N(R ^e )(R ^f ), and O(R ^e ), and L is -CH=CH- or - C≡C-. 69. The compound of embodiment 68, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -CH=CH-. 70. The compound of embodiment 69, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein L is -C≡C-. 71. A compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof,

thereof. 72. A pharmaceutical composition, comprising (i) a compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and (ii) a pharmaceutically acceptable carrier, diluent, or excipient. 73. A compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, for use in medical therapy. 74. A compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, for use in the treatment and/or prophylaxis of acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 75. A method for treating cancer in a mammal, comprising administering a compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal. 76. A compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, for use in modulating TEAD activity. 77. A compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, for use in the treatment and/or prophylaxis of a disease or condition mediated by TEAD activity. 78. The compound for the use of embodiment 77, wherein the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 79. The use of a compound as described in any one of embodiments 40-71, or a stereoisomer, automer, or pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of prophylaxis of a disease or condition that is mediated by TEAD activity. 80. The use of embodiment 79, wherein the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 81. A method for modulating TEAD activity, comprising contacting TEAD with a compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. 82. A method for treating a disease or condition mediated by TEAD activity in a mammal, comprising administering a compound as described in any one of embodiments 40-71, or a pharmaceutically acceptable salt thereof, to the mammal. 83. The method of embodiment 82, wherein the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 84. The use of a compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, for modulating TEAD activity. 85. The use of a compound as described in any one of embodiments 40-71, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, for the treatment and/or prophylaxis of a disease or condition mediated by TEAD activity. 86. The use of embodiment 85, wherein the disease or condition is acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing’s tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom’s macroglobulinemia, testicular tumors, uterine cancer and Wilms’ tumor. 87. A process for preparing a compound of formula (C): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, comprising converting an amino (NH2) group to an amide (NHC(O)R1) group using an acyl chloride compound . 88. A compound prepared by the process of embodiment 87. PREPARATION OF COMPOUNDS [0350] The following synthetic reaction schemes detailed in the General Schemes and Examples are merely illustrative of some of the methods by which the compounds of the present disclosure (or an embodiment or aspect thereof) can be synthesized. Various modifications to these synthetic reaction schemes can be made and will be suggested to one skilled in the art having referred to the disclosure contained in this Application. [0351] The starting materials and reagents used in preparing these compounds generally are either available from commercial suppliers, such as Aldrich Chemical Co., or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser’s Reagents for Organic Synthesis; Wiley & Sons: New York, 1991, Volumes 1- 15; Rodd’s Chemistry of Carbon Compounds, Elsevier Science Publishers, 1989, Volumes 1-5 and Supplementals; and Organic Reactions, Wiley & Sons: New York, 1991, Volumes 1-40. [0352] The starting materials and the intermediates of the synthetic reaction schemes can be isolated and purified if desired using conventional techniques, including but not limited to, filtration, distillation, crystallization, chromatography, and the like. Such materials can be characterized using conventional means, including physical constants and spectral data. [0353] Unless specified to the contrary, the reactions described herein preferably are conducted under an inert atmosphere at atmospheric pressure at a reaction temperature range of from about -78 ^C to about 150 ^C, more preferably from about 0 ^C to about 125 ^C. [0354] Although certain exemplary embodiments are depicted and described herein, the compounds of the present disclosure (or an embodiment or aspect thereof) can be prepared using appropriate starting materials according to the methods described generally herein and/or by methods available to one of ordinary skill in the art. [0355] Intermediates and final compounds were purified by either flash chromatography, and/or by reverse-phase preparative HPLC (high performance liquid chromatography), and/or by supercritical fluid chromatography, and/or by Preparative Thin Layer Chromatography (Prep TLC). [0356] Mass spectrometry (MS) was performed using a (1) Sciex 15 mass spectrometer in ES+ mode, or (2) Shimadzu liquid chromatography-mass spectrometry (LCMS) 2020 mass spectrometer in ESI+ mode. Mass spectra data generally only indicates the parent ions unless otherwise stated. MS or HRMS data is provided for a particular intermediate or compound where indicated. [0357] Nuclear magnetic resonance spectroscopy (NMR) was performed using a (1) Bruker AV III 300 NMR spectrometer, (2) Bruker AV III 400 NMR spectrometer, or (3) Bruker AV III 500 NMR spectrometer, and referenced to tetramethylsilane. NMR data is provided for a particular intermediate or compound where indicated. [0358] All reactions involving air-sensitive reagents were performed under an inert atmosphere. Reagents were used as received from commercial suppliers unless otherwise noted. [0359] The following generalized schemes are used to prepare the disclosed compounds, intermediates, and pharmaceutically acceptable salts thereof. Disclosed compounds and intermediates may be prepared using standard organic synthetic techniques and from comerically available starting materials and reagents. It will be appreciated that synthetic procedures employed in the preparation of disclosed compounds and intermediates will depend on the particular substituents present in the compound or intermediate and that various protection, deprotection, and conversion steps that are standard in organic synthesis may be required, but may not be illustrated in the following general schemes. It is also to be understood that any of the steps shown in any of the following general schemes may be used in any combination and in any order that is chemically feasible to achieve a desired intermediate or disclosed compound. [0360] SCHEME 1 [0361] Scheme 1 describes a general synthetic route for converting a -CH2-halo group to a -CH=CHR2 moiety using a phosphate compound and an aldehyde compound. R2, R3, X1, X2, and X ₃ are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). Halo refers to any halogen. In some embodiments, the halogen is chlorine, bromine, or iodine. In some embodiments, the phosphate compound is P(ORy)3, wherein Ry is any suitable atom or group, including, for example, C _1-8 alkyl. In certain variations, the phosphate compound is P(OEt) ₃ . The moiety may be any suitable atom or group, including, for example: a halogen, such a chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO ₂ . [0362] SCHEME 2 [0363] Scheme 2 describes a general synthetic route for converting a -CH2-OH group to a -CH=CHR2 moiety using a phosphate compound and an aldehyde compound. R2, R3, X1, X2, and X ₃ are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). Halo refers to any halogen. In some embodiments, the halogen is chlorine, bromine, or iodine. In some embodiments, the phosphate compound is P(ORy)3, wherein Ry is any suitable atom or group, including, for example, C1-8 alkyl. In certain variations, the phosphate compound is P(OEt)3. The moiety may be any suitable atom or group, including, for example: a halogen, such a chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO ₂ . [0364] SCHEME 3 [0365] Scheme 3 describes a general synthetic route for converting a halogen (halo) group to a -CH=CHR2 moiety using a boronic acid or a boronic ester compound. Halo refers to any halogen. In some embodiments, the halogen group is chlorine, bromine, or iodine. R ₂ , R ₃ , X ₁ , X ₂ , and X ₃ are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). R" may be any suitable atom or group, including, for example, hydrogen. In certain embodiments, the R" substituents, together with the atoms to which they are attached, may form a ring structure. In some embodiments, the compound of formula . The moiety may be any suitable atom or group, including, for example, a halogen, such as chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO2. [0366] SCHEME 4 [0367] Scheme 4 describes a general synthetic route for converting a halogen (halo) group to the -L-R ₂ moiety defined above for formulae (A), (B), (B-1), (C), (C-1), or (I), using a halo compound. Halo refers to any halogen. In some embodiments, the halogen is chlorine, bromine, or iodine. R2, R3, X1, X2, and X3 are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example, a halogen, such as chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO ₂ . [0368] SCHEME 5 [0369] Scheme 5 describes a general synthetic route for converting a halogen (halo) group to the R2 moiety defined above for formulae (A), (B), (B-1), (C), (C-1), or (I), using a boronic acid or a boronic ester compound. Halo refers to any halogen. In some embodiments, the halogen group is chlorine, bromine, or iodine. R ₂ , R ₃ , X ₁ , X ₂ , and X ₃ are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). R" may be any suitable atom or group, including, for example, hydrogen. The moiety may be any suitable atom or group, including, for example, a halogen, such as chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO ₂ . [0370] SCHEME 6 [0371] Scheme 6 describes a general synthetic route for converting a -CH2-halo group to a -CH ₂ -O-R ₂ moiety using a halo compound. Halo refers to any halogen. In some embodiments, the halogen is chlorine, bromine, or iodine. R ₂ , R ₃ , X ₁ , X ₂ , and X ₃ are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example, a halogen, such as chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO2. [0372] SCHEME 7 [0373] Scheme 7 describes a general synthetic route for converting a halogen (halo) group to an amino (NH2) moiety. Halo refers to any halogen. In some embodiments, the halogen is chlorine, bromine, or iodine. R3, X1, X2, and X3 are as defined above for formulae (A), (B), (B- 1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: a halogen, such as chlorine, bromine, or iodine; or the -L-R ₂ moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). In one embodiment, the halogen (halo) group is converted to the amino (NH ₂ ) moiety in the presence of a suitable catalyst such as CuI, a suitable base base such as K ₃ PO ₄ , and NH ₃ ·H ₂ O, and N ¹ ,N ² -bis(5-methyl-[1,1'-biphenyl]-2-yl)oxalamide. [0374] SCHEME 8 [0375] Scheme 8 describes a general synthetic route for converting an amino (NH ₂ ) group to an amide (NHC(O)R1) group using an acyl chloride compound. R1, R3, X1, X2, and X3 are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: a halogen, such as chlorine, bromine, or iodine; or the -L- R2 moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). [0376] SCHEME 9 [0377] Scheme 9 describes a general synthetic route for converting an amino (NH ₂ ) group to an amide (NHC(O)R1) group using an acyl chloride compound. R1, R3, X1, X2, and X3 are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: a halogen, such as chlorine, bromine, or iodine; or the -L- R2 moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). [0378] SCHEME 10 [0379] Scheme 10 describes a general synthetic route for converting a halogen (halo) group to an amino (NH2) group using an imine compound. R3, X1, X2, and X3 are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). R' is any suitable atom or group, including, for example, C _6-20 aryl. The moiety may be any suitable atom or group, including, for example: a halogen, such as chlorine, bromine, or iodine; or the -L-R2 moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). [0380] SCHEME 11 [0381] Scheme 11 describes a general synthetic route for converting an amino (NH2) group to the moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). R ₃ , X ₁ , X ₂ , and X ₃ are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: a halogen, such as chlorine, bromine, or iodine; or the -L-R2 moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). In one embodiment, the amino (NH ₂ ) moiety is converted to the moiety in the presence ethylmorpholine. [0382] SCHEME 12 [0383] Scheme 12 describes a general synthetic route for forming a compound of formulae (A), (B), (B-1), (C), (C-1), or (I) wherein R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl, provided that X3 is CH. X2 and X3 are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: a halogen, such as chlorine, bromine, or iodine; or the -L-R ₂ moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: H; a halogen, such a chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO2. In one embodiment, the three steps outlined in Scheme 12 are carried out sequentially in the presence of (i) a suitable electrophile such as , (ii) a utiable acid such as diethylaluminum chloride, and (iii) a suitable acid such as aluminum trifluoromethanesulfonate (aluminum triflate). [0384] SCHEME 13 [0385] Scheme 13 describes a general synthetic route for forming a compound of formulae (A), (B), (B-1), (C), (C-1), or (I) wherein R ₃ is taken together with R ₅ of X ₁ , and the atoms to which they are attached, to form a 5-membered heterocyclyl, provided that X3 is CH. X2 and X3 are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: a halogen, such as chlorine, bromine, or iodine; or the -L-R ₂ moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: H; a halogen, such a chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO2. In one embodiment, the three steps outlined in Scheme 13 are carried out sequentially in the presence of (i) a suitable electrophile such as 2-bromo-1,1-diethoxyethane, (ii) a suitable acid such as phenylpropanolamine (PPA), and (iii) a suitable catalyst such as Rh/C. [0386] SCHEME 14 [0387] Scheme 14 describes a general synthetic route for forming a compound of formulae (A), (B), (B-1), (C), (C-1), or (I) wherein R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heteroaryl, provided that X ₃ is CH. X ₂ and X ₃ are as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: C1-6alkyl, such as methyl; a halogen, such as chlorine, bromine, or iodine; or the -L-R2 moiety as defined above for formulae (A), (B), (B-1), (C), (C-1), or (I). The moiety may be any suitable atom or group, including, for example: H; a halogen, such a chlorine, bromine, or iodine; or -NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO ₂ . In one embodiment, the three steps outlined in Scheme 14 are carried out sequentially in the presence of (i) a suitable acid such as HNO3, (ii) a suitable catalyst such as Fe, and (iii) a suitable nucleophile such as NH ₄ Cl. [0388] SCHEME 15 [0389] Scheme 15 describes a general synthetic route for forming a compound of formula (B) or formula (C) wherein R1 is oxetanyl, wherein the oxetanyl is optionally substituted with one or more C _1-6 alkyl. In some embodiments, R _c is H. In other embodiment, R _c is methyl. H ⁺ is any suitable acid, including, for example trifluoroacetic acid (TFAA). [0390] SCHEME 16 [0391] Scheme 16 describes a general synthetic route for forming a compound of formula (B) or formula (C) wherein R ₁ is oxetanyl, wherein the oxetanyl is optionally substituted with one or more C1-6alkyl. In some embodiments, Rc is H. In other embodiments, Rc is methyl. [0392] SCHEME 17 [0393] Scheme 17 describes a general synthetic route for forming a compound of formula (B) or formula (C) wherein R ₁ is N(CN)(R ^e ). In some embodiments, R ^e is H. In other embodiments, R ^e is C1-6alkyl. In still other embodiments, R ^e is methyl. Any acceptable base may be used, including, for example, sodium hydroxide. [0394] Disclosed herein are certain intermediates, including compounds having the structure of formula (II): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. R _y is any suitable atom or group, including, for example, C _1-8 alkyl. In certain variations, R _y is ethyl. The moiety may be any suitable atom or group, including, for example: a halogen, such a chlorine, bromine, or iodine; the -NHC(O)R1 moiety as described in formulae (A), (B), (B-1), (C), (C-1), or (I); or - NR ^s R ^t , wherein R ^s and R ^t are each independently any suitable atom or group, including, for example, a protecting group. In some variations, R ^s and R ^t are different. In other variations, R ^s and R ^t are the same. In one embodiment, -NR ^s R ^t is -NO2. [0395] In other embodiments, disclosed herein are Intermediates A-M, as described in the Examples below. EXAMPLES INTERMEDIATE A [0396] Preparation of trans-4-(trifluoromethyl)cyclohexanecarbaldehyde [0397] The general reaction scheme was as follows: [0398] Step 1: Trans-N-methoxy-N-methyl-4-(trifluoromethyl)cyclohexanecarbo xamide [0399] To a mixture of trans-4-(trifluoromethyl)cyclohexanecarboxylic acid (50.0 g, 0.250 mol) and 1 drop of DMF in DCM (500 mL) was added oxalyl chloride (33.0 mL, 0.380 mol) dropwise at 0°C. The resulting mixture was stirred at 0°C for 2 hours. The reaction mixture was concentrated to afford trans-4-(trifluoromethyl)cyclohexanecarbonyl chloride (54.0 g, 99%) as a white solid which was used in the next step directly without further purification. To a mixture of N,O-dimethylhydroxylamine hydrochloride (73.6 g, 0.750 mmol) and N,N- diisopropylethylamine (35.8 g, 0.270 mmol) in DCM (500 mL) was added trans-4- (trifluoromethyl)cyclohexanecarbonyl chloride (54.0 g, 0.250 mmol) dissolved in DCM (100 mL) dropwise at 0°C. The reaction mixture was stirred at 0°C for 3 hours then the reaction mixture was diluted with saturated aqueous citric acid solution (500 mL) and extracted with DCM (500 mL × 2). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (0 - 30 % EtOAc in petroleum ether) to afford the title compound (56.0 g, 93%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 3.71 (s, 3H), 3.19 (s, 3H), 2.68 - 2.65 (m, 1H), 2.08 - 2.02 (m, 3H), 1.93 - 1.89 (m, 2H), 1.59 - 1.53 (m, 2H), 1.40 - 1.36 (m, 2H). [0400] Step 2: Trans-4-(trifluoromethyl)cyclohexanecarbaldehyde [0401] To a mixture of trans-N-methoxy-N-methyl-4- (trifluoromethyl)cyclohexanecarboxamide (5.00 g, 20.9 mmol) in DCM (50 mL) was added DIBAL-H (1.0 M in toluene, 62.7 mL, 62.7 mmol) dropwise at -78°C and then stirred for further 2 hours at -78°C. The reaction was then quenched with MeOH (5.0 mL) and water (5.0 mL). The reaction mixture was warmed to room temperature, dried over MgSO _4, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (2.80 g, 74%) as a light yellow oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 9.72 - 9.53 (m, 1H), 2.29 - 1.95 (m, 6H), 1.44 - 1.21 (m, 4H). INTERMEDIATE B [0402] Preparation of 4,4-Difluorocyclohexanecarbaldehyde [0403] The general reaction scheme was as follows: [0404] A stirred solution of ethyl 4,4-difluorocyclohexanecarboxylate (10.0 g, 52.0 mmol) in DCM (200 mL) was added DIBAL-H (1.0 M in toluene, 47.0 mL, 47.0 mmol,) dropwise at -78°C. The reaction mixture was stirred at -78 °C for 2 hours. The reaction was quenched with MeOH (5.0 mL) and water (5.0 mL). The reaction mixture was warmed to room temperature, dried over Mg ₂ SO ₄ , filtered and concentrated to afford the title compound (8.00 g, 83%) as light yellow oil which was used in the next step directly without further purification. ¹ H NMR (400 MHz, CDCl3): δ 9.66 (s, 1H), 2.33 - 2.28 (m, 1H), 2.02 - 1.94 (m, 4H), 1.88 - 1.79 (m, 4H). INTERMEDIATE C [0405] Preparation of 2-Chloro-5-methoxy-4-((E)-2-(trans- (trifluoromethyl)cyclohexyl)vinyl)pyridine [0406] The general reaction scheme was as follows: [0407] Step 1: 2-Chloro-5-methoxypyridine [0408] A solution of 6-chloropyridin-3-ol (89.0 g, 0.69 mol) in DMF (500 mL) was added NaH (60 wt% in mineral oil, 40.0 g, 1.00 mol) at 0°C. The reaction solution was stirred at 0°C for 30 minutes and a solution of iodomethane (49.0 mL, 0.79 mol) in DMF (50.0 mL) was added. The mixture was stirred at room temperature for 16 hours at which point the reaction was quenched with saturated aqueous NH4Cl (500 mL) and extracted with EtOAc (400 mL × 3). The organic layers were combined, washed with water (300 mL × 3), dried over Na ₂ SO ₄ and concentrated to dryness in vacuo. The residue was purified by flash column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (82.0 g, 83%) as a colorless oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.04 (d, J = 2.8 Hz, 1H), 7.24 - 7.15 (m, 2H), 3.83 (s, 3H); LCMS (ESI): m/z 143.8 (M+H) ⁺ . [0409] Step 2: 2-Chloro-5-methoxyisonicotinaldehyde [0410] To a a mixture of 2-chloro-5-methoxy-pyridine (25.0 g, 0.17 mol) in THF (250 mL) was added LDA (2.0 M in THF, 175 mL, 0.35 mol) at -78°C. The reaction was stirred at - 78°C for 20 minutes. DMF (27.0 mL, 0.35 mol) was added to the reaction mixture at -78°C, and the mixture was stirred for another 1 hour. The reaction was quenched with saturated aqueous NH ₄ Cl solution (100 mL), extracted with EtOAc (400 mL × 3, dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 25% EtOAc in petroleum ether) to afford the title compound (24.0 g, 80%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 10.41 (s, 1H), 8.28 (s, 1H), 7.59 (s, 1H), 4.05 (s, 3H). [0411] Step 3: (2-Chloro-5-methoxypyridin-4-yl)methanol [0412] A flask was charged with 2-chloro-5-methoxyisonicotinaldehyde (26.0 g, 0.150 mol), diluted with methanol (250 mL) and cooled to 0°C. At which point NaBH4 (7.00 g, 0.190 mol) was added slowly and the reaction mixture was stirred for 3 hours. The reaction solution was diluted with water (200 mL) and extracted with EtOAc (200 mL × 3). The organic layers were combined, dried over Na2SO4 and concentrated to afford the title compound (24.0 g, 91%) as a white solid. ¹ H NMR (400 MHz, CD ₃ OD): δ 7.97 (s, 1H), 7.45 (s, 1H), 4.87 (s, 2H), 3.93 (s, 3H). [0413] Step 4: 4-(Bromomethyl)-2-chloro-5-methoxypyridine [0414] To the mixture of (2-chloro-5-methoxypyridin-4-yl)methanol (24.0 g, 0.140 mol) in DCM (240 mL) was added tribromo phosphine (4.50 mL, 47.4 mmol) at 0 °C. The reaction was stirred at room temperature for 2 h. The solution was concentrated and the residue was purified by column chromatography on silica gel (0 - 20% EtOAc in petroleum ether) to afford the title compound (18.0 g, 55%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.01 (s, 1H), 7.31 (s, 1H), 4.40 (s, 2H), 3.99 (s, 3H). [0415] Step 5: Diethyl ((2-chloro-5-methoxypyridin-4-yl)methyl)phosphonate [0416] A mixture of 4-(bromomethyl)-2-chloro-5-methoxypyridine (23.0 g, 97.3 mmol) and triethyl phosphite (30.0 mL, 0.51 mol) were stirred at 130°C for 3 hours under reflux. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (0 - 50% EtOAc in petroleum ether) to afford the title compound (27.0 g, 95%) as a colorless oil. ¹ H NMR (400 MHz, CDCl3): δ 7.93 (s, 1H), 7.24 (d, J = 2.8 Hz, 1H), 4.07 - 4.00 (m, 4H), 3.93 (s, 3H), 3.19 (d, J = 22.8 Hz, 2H), 1.26 (t, J = 7.2 Hz, 6H). [0417] Step 6: 2-Chloro-5-methoxy-4-((E)-2-(trans- (trifluoromethyl)cyclohexyl)vinyl)pyridine [0418] To a solution of diethyl ((2-chloro-5-methoxypyridin-4-yl)methyl)phosphonate (12.0 g, 40.8 mmol) in toluene (180 mL) was added sodium tert-pentoxide (5.85 g, 53.1 mmol) at 0°C. After mixture was stirred at 0°C for 20 minutes a solution of trans-4- (trifluoromethyl)cyclohexanecarbaldehyde (14.7 g, 81.7 mmol) in THF (180 mL) was added dropwise. The reaction mixture was stirred for 1.5 hours at 0°C. Upon completion of the reaction, it was poured into saturated aqueous NH ₄ Cl solution (200 mL) and extracted with EtOAc (200 mL × 2). The organic layers were combined, washed with brine (200 mL), dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (12 g, 92%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.93 (s, 1H), 7.24 (s, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.33 (dd, J = 16.0, 6.8 Hz, 1H), 3.90 (s, 3H), 2.17 - 2.13 (m, 1H), 2.04 - 1.95 (m, 5H), 1.43 - 1.36 (m, 2H), 1.24 - 1.20 (m, 2H). INTERMEDIATE D [0419] Preparation of 5-Methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-amine [0420] The general reaction scheme was as follows: [0421] Step 1: 5-Methoxy-4-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl)viny l)pyridin- 2-amine [0422] To a solution of 2-Chloro-5-methoxy-4-((E)-2-(trans- (trifluoromethyl)cyclohexyl)vinyl)pyridine (4.00 g, 12.51 mmol) in DMSO (40 mL) added CuI (239 mg, 1.25 mmol), K ₃ PO ₄ (1.00 g, 37.53 mmol), NH ₃ ^. H ₂ O (1.9 mL, 101.53 mmol, 25%wt) and N ¹ ,N ² -bis(5-methyl-[1,1'-biphenyl]-2-yl)oxalamide (526 mg, 1.25 mmol). The solution was stirred at 110°C for 16 hours under a nitrogen atmosphere. The reaction mixture was diluted with water (100 ml) and extracted with EtOAc (100 mL × 2). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 50% EtOAc in petroleum ether) to afford the title compound (2.80 g, 75%) as a brown solid. ¹ H NMR (400 MHz, DMSO-d6): δ 7.75 (s, 1H), 6.52 (s, 1H), 6.46 (d, J = 16.4 Hz, 1H), 6.26 (dd, J = 16.4, 6.8 Hz, 1H), 5.39 (s, 2H), 3.71 (s, 3H), 2.23 - 2.13 (m, 2H), 1.92 - 1.83 (m, 4H), 1.34 - 1.21 (m, 4H). INTERMEDIATE E [0423] Preparation of (E)-4-(2-(4,4-Difluorocyclohexyl)vinyl)-5-methoxypyridin-2- amine [0424] The general reaction scheme was as follows: [0425] Step 1: (E)-2-Chloro-4-(2-(4,4-difluorocyclohexyl)vinyl)-5-methoxypy ridine [0426] The title compound (4.00 g, 81%) was furnished as a colorless oil. It was prepared from diethyl ((6-chloro-3-methoxypyridazin-4-yl)methyl)phosphonate diethyl ((2- chloro-5-methoxypyridin-4-yl)methyl)phosphonate (5.00 g, 17.0 mmol) and 4,4- difluorocyclohexanecarbaldehyde (Intermediate 2, 5.00 g, 34.0 mmol) following the procedure outlined for Intermediate C, Step 6. ¹ H NMR (400 MHz, CDCl3): δ 7.96 (s, 1H), 7.29 (s, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 6.8 Hz, 1H), 3.92 (s, 3H), 2.30 - 2.29 (m, 1H), 2.18 - 2.12 (m, 2H), 1.88 - 1.84 (m, 2H), 1.79 - 1.71 (m, 2H), 1.63 - 1.57 (m, 2H). [0427] Step 2: (E)-4-(2-(4,4-Difluorocyclohexyl)vinyl)-5-methoxypyridin-2-a mine [0428] The title compound (250 mg, 53%) was furnished as a brown solid. It was prepared from (E)-2-chloro-4-(2-(4,4-difluorocyclohexyl)vinyl)-5-methoxypy ridine (500 mg, 1.74 mmol) following the procedure outlined for Intermediate D. ¹ H NMR (400 MHz, CDCl3): δ 7.27 - 7.23 (m, 2H), 6.59 (d, J = 16.0 Hz, 1H), 6.30 (dd, J = 16.0, 7.2 Hz, 1H), 4.23 (br s , 2H), 3.83 (s, 3H), 2.43 - 2.35 (m, 1H), 2.35 - 2.23 (m, 2H), 2.16 - 2.13 (m, 2H), 2.00 - 1.88 (m, 2H), 1.65 - 1.51 (m, 2H). INTERMEDIATE F [0429] Preparation of 6-Methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-amine [0430] The general reaction scheme was as follows: [0431] Step 1: 5-Bromo-2-methoxy-3-((E)-2-(trans-4 (trifluoromethyl)cyclohexyl)vinyl)pyridine [0432] To a solution of diethyl ((5-bromo-2-methoxypyridin-3-yl)methyl)phosphonate (1.15 g, 3.41 mmol) in toluene (15.0 mL) was added sodium tert-pentoxide (0.490 g, 4.43mmol) at 0°C. After being stirred at 0°C for 20 minutes, a solution of trans-4-(trifluoromethyl) cyclohexanecarbaldehyde (Intermediate 1, 1.23 g, 6.81 mmol) in THF (15.0 ml) was added dropwise and the reaction mixture was stirred for 1.5 hours at 0°C. The reaction mixture was poured into saturated aqueous NH4Cl solution (50 mL) and extracted with EtOAc (100 mL × 2). The combined organic layers were washed with brine (50 ml), dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (1.04 g, 83%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 2.0 Hz, 1H), 7.72 (d, J = 2.0 Hz, 1H), 6.48 (d, J = 16.0 Hz, 1H), 6.20 (dd, J = 16.0, 6.8 Hz, 1H), 3.95 (s, 3H), 2.16 - 2.10 (m, 1H), 2.08 - 1.92 (m, 5H), 1.48 - 1.33 (m, 2H), 1.31 - 1.16 (m, 2H). [0433] Step 2: 6-Methoxy-5-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl)viny l)pyridin- 3-amine [0434] To a solution of 5-bromo-2-methoxy-3-((E)-2-(trans-4 (trifluoromethyl)cyclohexyl)vinyl)pyridine (930 mg, 2.55 mmol) in DMSO (16 mL) was added CuI (48.0 mg, 0.26 mmol), K ₃ PO ₄ (2.04g, 7.66 mmol), NH ₃ ^. H ₂ O (0.570 ml, 7.66 mmol, 25%wt) and N ¹ ,N ² -bis(5-methyl-[1,1'-biphenyl]-2-yl)oxalamide (107 mg, 0.26 mmol). The reaction mixture was stirred at 110°C for 16 hours. The reaction was diluted with water (50 mL), extracted with EtOAc (50 mL × 3) and the combined organic layers were dried with Na ₂ SO ₄ and concentrated. The residual was purified by column chromatography on silica gel (0 - 2% EtOAc in petroleum ether) to afford the title compound (620 mg, 80%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.52 (d, J = 2.4 Hz, 1H), 7.08 (d, J = 2.4 Hz, 1H), 6.51 (d, J = 16.0 Hz, 1H), 6.14 (d, J = 16.0, 6.8 Hz, 1H), 3.89 (s, 3H), 3.32 (s, 2H), 2.10 - 2.05 (m, 1H), 2.03 - 1.91 (m, 5H), 1.44 - 1.09 (m, 4H); LCMS (ESI): m/z 301.2 (M+H) ⁺ . INTERMEDIATE G [0435] Preparation of (E)-5-(2-(4,4-Difluorocyclohexyl)vinyl)-6-methoxypyridin-3- amine [0436] The general reaction scheme was as follows: [0437] Step 1: (E)-5-Bromo-3-(2-(4,4-difluorocyclohexyl)vinyl)-2-methoxypyr idine [0438] The title compound (2.66 g, 78%) was furnished as a white solid. It was prepared from diethyl ((5-bromo-2-methoxypyridin-3-yl)methyl)phosphonate (3.00 g, 8.90 mmol) and 4,4-difluorocyclohexanecarbaldehyde (Intermediate 2, 2.64 g, 17.8 mmol) following the procedure outlined for Intermediate F, Step 1. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.05 (d, J = 2.0 Hz, 1H), 7.72 (d, J = 2.0 Hz, 1H), 6.51 (d, J = 16.4 Hz, 1H), 6.21 (dd, J = 16.4, 7.2 Hz, 1H), 3.95 (s, 3H), 2.32 - 2.22 (m, 1H), 2.21 - 2.04 (m, 2H), 1.93 - 1.82 (m, 4H), 1.63 - 1.54 (m, 2H). [0439] Step 2: (E)-5-(2-(4,4-Difluorocyclohexyl)vinyl)-6-methoxypyridin-3-a mine [0440] The title compound (544 mg, 67%) was furnished as a white solid. It was prepared from (E)-5-bromo-3-(2-(4,4-difluorocyclohexyl)vinyl)-2-methoxypyr idine (1.00 g, 3.01 mmol) and following the procedure outlined for Intermediate F, Step 2. ¹ H NMR(400 MHz, DMSO-d ₆ ): δ 7.40 (d, J = 2.4 Hz, 1H), 7.11 (d, J = 2.4 Hz, 1H), 6.44 (d, J = 16.0 Hz, 1H), 6.16 (dd, J = 16.0, 8.0 Hz, 1H), 4.71 (s, 2H), 3.74 (s, 3H), 2.36 - 2.29 (m, 1H), 2.12 - 1.96 (m, 2H), 1.94 - 1.88 (m, 1H), 1.86 - 1.74 (m, 3H), 1.51 - 1.31 (m, 2H). INTERMEDIATE H [0441] Preparation of (E)-4-(2-(4,4-Difluorocyclohexyl)vinyl)-5-methoxypyridin-2- amine [0442] The general reaction scheme was as follows: [0443] To a mixture of 5-bromo-2-methoxy-3-methylpyridine (3.00 g, 14.93 mmol) in CCl4 (20 mL) was added (E)-2,2'-(diazene-1,2-diyl)bis(2-methylpropanenitrile) (36 mg, 0.22 mmol) NBS (2.92 g, 16.42 mmol). The reaction was stirred at 80°C for 2 hours. The reaction was then filtered and the filtrate was concentrated under reduced pressure to afford the title compound (2.70 g, 64%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 2.4 Hz, 1H), 7.72 (d, J = 2.4 Hz, 1H), 4.42 (s, 2H), 3.99 (s, 3H). INTERMEDIATE I [0444] Preparation of 4,4,5,5-Tetramethyl-2-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)-1,3,2-dioxaborolane [0445] Preparation of a stock solution of LiTMP: To a solution of 2,2,6,6- tetramethylpiperidine (11.76 g, 83.25 mmol) in THF (50 mL) was added n-BuLi (33.3 mL, 83.25 mmol, 2.5 mol/L) at -78 ^o C dropwise. [0446] To a solution of bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methane (17.85 g, 66.6 mmol) in THF (100 mL) was added the solution LiTMP at -78 ^o C dropwise. The mixture was stirred for 30 minutes at -78°C. Trans-4-(trifluoromethyl)cyclohexanecarbaldehyde (Intermediate 1, 10.0 g, 55.5 mmol) in THF (30 mL) was added at -78°C dropwise. The mixture was stirred at -78°C for 2 hours. The reaction was quenched with water (200 mL). The mixture was extracted with ethyl acetate (200 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by flash column chromatography on silica gel (0 - 2% ethyl acetate in petroleum ether) to afford the title compound (9.2 g, 55%, ~10% cis isomer) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 6.54 (dd, J = 18.4, 6.4 Hz, 1H), 5.41 (d, J = 18.4 Hz, 1H), 2.01 - 1.87 (m, 6H), 1.40 - 1.33 (m, 2H), 1.27 (s, 12H), 1.18 - 1.08 (m, 2H). INTERMEDIATE J [0447] Preparation of 7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-amine [0448] The general reaction scheme was as follows: [0450] A mixture of 2,6-dibromophenol (525 g, 2.08 mol), NaOH (91.7 g, 2.29 mol) and 1,2-dibromoethane (180.43 mL, 2.08 mol) in water (1.5L) was stirred at 100 ^o C for 16 hours. After cooling to room temperature, the oil product was separated via a separation funnel, washed with NaOH (1M) (200 mL × 2) to remove the starting materials. The product was dissolved in petroleum ether (800 mL), dried over Na2SO4, filtered and concentrated to afford the title compound (520 g, 69%) as a yellow liquid. ¹ H NMR (400 MHz, DMSO-d6): δ 7.68 (dd, J = 8.0, 2.4 Hz, 2H), 7.07 (t, J = 8.0 Hz, 1H), 4.28 (t, J = 5.6 Hz, 2H), 3.85 (t, J = 5.6 Hz, 2H). [0451] Step 2: Preparation of 7-bromo-2,3-dihydrobenzofuran [0452] To a mixture of 1,3-dibromo-2-(2-bromoethoxy)benzene (200 g, 557.34 mmol) in THF (1.5 L) was added n-BuLi (227.39 mL, 568.48mmol, 2.5 mol/L in hexane) at -78°C dropwise. The mixture was stirred at -78°C for 1 hour. The reaction was quenched by water (500 mL). The mixture was diluted with water (1 L), extracted with ethyl acetate (1 L × 2) and the organic layers were combined. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to afford the title compound (100 g, 90%) as a colorless oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.30 - 7.23 (m, 1H), 7.10 (dd, J = 7.2, 1.2 Hz, 1H), 6.71 (t, J = 7.6 Hz, 1H), 4.65 (t, J = 8.8 Hz, 2H), 3.30 (t, J = 8.8 Hz, 2H). [0453] Step 3: Preparation of 7-bromo-5-nitro-2,3-dihydrobenzofuran [0454] To a mixture of 7-bromo-2,3-dihydrobenzofuran (100 g, 502.41 mmol) in DCM (1 L) at 0°C was added a mixture solution of con. aq. H2SO4 (70 mL) and con. aq. HNO3 (68.6 mL). The mixture was stirred at 0°C for 30 min. The mixture was quenched with water (500 mL), carefully adjusted pH to 9 with 25% NaOH solution and extracted with EtOAc (1 L × 3). The organic layer was washed with water (1 L × 3), dried over Na2SO4, filtered and concentrated to afford the tile compound (98 g, 80%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.30 (d, J = 2.4 Hz, 1H), 8.04 (d, J = 2.4 Hz, 1H), 4.85 (t, J = 8.8 Hz, 2H), 3.43 (t, J = 8.8 Hz, 1H). [0455] Step 4: Preparation of 7-bromo-2,3-dihydrobenzofuran-5-amine [0456] A solution of 7-bromo-5-nitro-2,3-dihydrobenzofuran (100 g, 409.77 mmol), NH4Cl (110 g, 2.05 mol) and iron powder (115 g, 2.05 mol) in water : ethanol (1:1) (2.5 L) was stirred at 80 ^o C for 3 hours. After cooling to room temperature, the reaction mixture was filtered and concentrated. Then the mixture was extracted with EtOAc (500 mL × 3 and the organic layer was washed with water (500 mL × 5). The organics were dried over Na2SO4, filtered and concentrated. The crude was dissolved in DCM (200 mL) and then petroleum ether (400 mL) was added. The solids where collected to afford the title compound (70.2 g, 80%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 6.64 (s, 1H), 6.53 (s, 1H), 4.59 (t, J = 8.8 Hz, 2H), 3.42 (br s, 2H), 3.23 (t, J = 8.8 Hz, 2H). [0457] Step 5: Preparation of 7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-amine [0458] A mixture of 7-bromo-2,3-dihydrobenzofuran-5-amine (100g, 467.16 mmol), (4- isopropylphenyl)boronic acid (78.15 g, 476.5 mmol), Pd(dppf)Cl2 (17.09 g, 23.36 mmol), Na ₂ CO ₃ (149 g, 1.41 mol) in 1,4-Dioxane (1L) and water (100 mL) was stirred at 100 ^o C for 2 hours under a N2 atmosphere. After being cooled to room temperature, the reaction mixture was filtered and the filtrate was concentrated under vacuum. The residue was purified by flash chromatography on silica gel (0 - 30% ethyl acetate in petroleum ether) to afford the title compound (116 g, 98%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.61 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 6.66 (d, J = 2.4 Hz, 1H), 6.59 (d, J = 2.4 Hz, 1H), 4.56 (t, J = 8.8 Hz, 2H), 3.18 (t, J = 8.8 Hz, 2H), 3.00 - 2.92 (m, 1H), 1.30 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 254.1 (M+H) ⁺ . INTERMEDIATE K [0459] Preparation of 4-bromo-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-amine [0460] The general reaction scheme was as follows: [0461] Step 1: Preparation of N-(7-(4-Isopropylphenyl)-2,3-dihydrobenzofuran-5- yl)acetamide [0462] To a solution of 7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-amine (150 g, 592.09 mmol) and TEA (99.03 mL, 710.51 mmol) in DCM (1.5 L) was added acetyl chloride (46.31 mL, 651.3 mmol) at -78°C dropwise. The reaction was stirred at -78°C for 2 hours. The reaction was quenched with water (200 mL) and extracted with dichloromethane (1 L × 2). The combined organic layers were dried over Na2SO4 and concentrated. The residue was triturated with DCM and hexanes (1:10) and filtered to afford the title compound (222 g, 83%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.58 (d, J = 8.0 Hz, 2H), 7.48 (s, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.21 (s, 1H), 7.19 (s, 1H), 4.60 (t, J = 8.8 Hz, 2H), 3.24 ( t, J = 8.8 Hz, 2H), 2.96 - 2.90 (m, 1H), 2.16 (s, 3H), 1.27 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 296.1 (M+H) ⁺ . [0463] Step 2: Preparation of N-(4-bromo-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran- 5-yl)acetamide [0464] A mixture of N-(7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)acetamid e (100 g, 338.55 mmol) and bromine (19.08 mL, 372.4 mmol) in Acetic acid (500 mL) was stirred at 50°C for 10 min. The reaction mixture was diluted with water (1 L) and the pH was adjusted to 7 with a 2M NaOH aqueous solution. The mixture was extracted with EtOAc (1 L × 3), the combined organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was dissolved in DCM (200 mL) and MTBE was added until a precipitate appears. The heterogenous mixture was cooled to 0°C for 20 minutes. Then the precipitate was filtered to afford the title compound (38 g, 30%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.09 (s, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 4.65 (t, J = 8.8 Hz, 2H), 3.28 (t, J = 8.8 Hz, 2H), 2.93 - 2.88 (m, 1H), 2.22 (s, 3H), 1.28 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 374.1 (M+H) ⁺ . [0465] Step 3: Preparation of 4-bromo-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5- amine [0466] A mixture of 12 M aqueous hydrochloric acid (334 mL, 4.01 mol) and N-(4- bromo-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)aceta mide (150 g, 400.78 mmol) in ethanol (1.5 L) was stirred at 80°C for 5 hours. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was diluted with water and the pH was adjusted to 9 with a 2 M NaOH aqueous solution. The mixture was extracted with EtOAc (1 L × 3), then the combined organic layers were dried over Na ₂ SO ₄ and evaporated to afford the title compound (124 g, 93%) as a brown solid. ¹ H NMR (400 MHz, CDCl3): δ 7.54 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.72 (s, 1H), 4.58 (t, J = 8.8 Hz, 2H), 3.78 (s, 2H), 3.23 (t, J = 8.8 Hz, 2H), 2.93 - 2.89 (m, 1H), 1.25 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 332.1 (M+H) ⁺ . INTERMEDIATE L [0467] Preparation of 5-amino-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-4- carbonitrile [0468] The general reaction scheme was as follows: [0469] A mixture of t-BuXPhos Pd G3 (19.0 g, 23.92 mmol), Zn(CN)2 (176.7 g, 1.51mol) and 4-bromo-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-amine (100 g, 301 mmol) in N,N-dimethylacetamide (1 L) was stirred at 140°C for 16 hours. After cooling to room temperature, the reaction solution was added into with water (2 L). The mixture solution was filtered and the filter cake was washed with water (2 L). The filter cake was dissolved in EtOAc (2 L), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography silica gel (0 - 50 % ethyl acetate in petroleum ether) to afford 80 g crude product. The crude product was triturated with DCM:hexanes (1:10) and filtered to afford the title compound (59g, 70%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 7.59 (dd, J = 8.0, 1.6 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.68 (s, 1H), 4.64 (t, J = 8.8 Hz, 2H), 4.08 (br s, 2H), 3.36 (t, J = 8.8 Hz, 2H), 2.97 - 2.95 (m, 1H), 1.28 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 279.1 (M+H) ⁺ . INTERMEDIATE M [0470] Preparation of 5-amino-7-chloro-2,3-dihydrobenzofuran-4-carbonitrile [0471] The general reaction scheme was as follows: [0472] Step 1: Preparation of 4-bromo-1-chloro-2-(2,2-diethoxyethoxy)benzene [0473] A mixture solution of 5-bromo-2-chloro-phenol (90 g, 433.8 mmol), K ₂ CO ₃ (90 g, 650.8 mmol) and 2-bromo-1,1-diethoxyethane (94 g, 477.2 mmol) in DMF (900 mL) was heated at 135°C for 16 hours. The reaction mixture was concentrated and diluted with EtOAc (600 mL) and washed with brine (500 mL × 5). The organic layer was dried over Na2SO4, filtered and concentrated to afford the title compound (140 g, 99%) as a brown oil. The crude was used for next step without further purification. ¹ H NMR (400 MHz, CDCl3): δ 7.22 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 2.0 Hz, 1H), 7.04 (dd, J = 8.4, 2.0 Hz, 1H), 4.87 (t, J = 5.2 Hz, 1H), 4.05 (d, J = 5.2 Hz, 2H), 3.87 - 3.76 (m, 2H), 3.73 - 3.62 (m, 2H), 1.26 (t, J = 7.2 Hz, 6H). [0474] Step 2: Preparation of 4-bromo-7-chlorobenzofuran [0475] The reaction mixture of 4-bromo-1-chloro-2-(2,2-diethoxyethoxy)benzene (140 g, 432.6 mmol) and PPA (140 g) in toluene (1.4 L) was heated at 110°C for 5 hours. The reaction mixture was quenched with sat. aq. NaHCO3 and extracted with EtOAc (1.0 L × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel (100% petroleum ether) to afford the title compound (44.0 g, 44%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 2.0 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 2.0 Hz, 1H). [0476] Step 3: Preparation of 4-bromo-7-chloro-2,3-dihydrobenzofuran [0477] A mixture of Rh/C (10.0 g, 95.0 mmol) and 4-bromo-7-chlorobenzofuran (44.0 g, 190 mmol) in EtOH (440 mL) was stirred at room temperature for 2 hours under atmosphere of H2 (15 psi). The reaction was filtered and the filtrate was concentrated. The residue was purified by chromatography on silica gel (100% petroleum ether) to afford the title compound (33.0 g, 74%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.01 (d, J = 8.8 Hz, 1H), 6.93 (d, J = 8.8 Hz, 1H), 4.72 (t, J = 8.8 Hz, 2H), 3.30 (t, J = 8.8 Hz, 2H). [0478] Step 4: Preparation of 4-bromo-7-chloro-5-nitro-2,3-dihydrobenzofuran [0479] To the mixture of 4-bromo-7-chloro-2,3-dihydrobenzofuran (30.0 g, 128.5 mmol) in TFA (300 mL) was added HNO3 (11.4 mL, 257.0 mmol) at 0°C dropwise slowly. The reaction mixture was stirred for 2 hours. At this point, the reaction mixture was quenched with aq.1M NaOH and the mixture was extracted with EtOAc (1.0 L × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (27.0 g, 76%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.97 (s, 1H), 4.88 (t, J = 8.8 Hz, 2H), 3.42 (t, J = 8.8 Hz, 2H). [0480] Step 5: Preparation of 7-chloro-5-nitro-2,3-dihydrobenzofuran-4-carbonitrile [0481] To a solution of 4-bromo-7-chloro-5-nitro-2,3-dihydrobenzofuran (12.0 g, 43.1 mmol) in DMF (100 mL) was added CuCN (8.0 g, 86.2 mmol). The mixture was stirred at 80°C for 16 hours. The reaction mixture was quenched with water (200 mL) and extracted with EtOAC (500 mL × 2). The combined organic layers were washed with brine (300 mL × 2), dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (5.3 g, 55%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.26 (s, 1H), 4.98 (t, J = 8.8 Hz, 2H), 3.64 (t, J = 8.8 Hz, 2H). [0482] Step 6: Preparation of 5-amino-7-chloro-2,3-dihydrobenzofuran-4-carbonitrile [0483] To a mixture of 7-chloro-5-nitro-2,3-dihydrobenzofuran-4-carbonitrile (5.3 g, 23.6 mmol) in HOAc (50 mL) was added Fe (6.6 g, 118.0 mmol). The mixture was stirred at 80°C for 2 hours. The reaction was adjusted to pH = 8 with sat. aq. NaHCO3 and extracted with EtOAc (300 mL × 2). The combined organics were dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash chromatography gel (0 - 10 % EtOAc in petroleum ether) to afford the title compound (4.0 g, 87%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 6.58 (s, 1H), 4.68 (t, J = 8.8 Hz, 2H), 4.10 (s, 2H), 3.38 (t, J = 8.8 Hz, 2H). LCMS (ESI): m/z 195.0 (M+H) ⁺ . [0484] INTERMEDIATE N [0485] Preparation of methyl 5-amino-7-chloro-2,3-dihydrobenzofuran-4-carboxylate [0486] The general reaction scheme was as follows: [0487] Step 1: Preparation of 4-bromo-1-chloro-2-(2,2-diethoxyethoxy)benzene [0488] The reaction mixture of 5-bromo-2-chlorophenol (90.0 g, 433.8 mmol), K2CO3 (90 g, 650.8 mmol) and 2-bromo-1,1-diethoxyethane (94.0 g, 477.2 mmol) in DMF (900 mL) was heated at 135°C for 16 hours. The reaction mixture was concentrated and diluted with EtOAc (1 L), washed with brine (1 L × 5). The organic layer was dried over Na2SO4, filtered and concentrated to afford the title compound (140.0 g, 99%) as a brown oil. The crude product was used for next step without further purification. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.22 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 2.0 Hz, 1H), 7.04 (dd, J = 8.4, 2.0 Hz, 1H), 4.87 (t, J = 5.2 Hz, 1H), 4.05 (d, J = 5.2 Hz, 2H), 3.83 - 3.76 (m, 2H), 3.73 - 3.68 (m, 2H), 1.26 (t, J = 7.2 Hz, 6H). [0489] Step 2: Preparation of 4-bromo-7-chlorobenzofuran [0490] The reaction mixture of 4-bromo-1-chloro-2-(2,2-diethoxyethoxy)benzene (140.0 g, 432.6 mmol) and PPA (140 g) in toluene (1.4 L) was heated at 110°C for 5 hours. The reaction mixture was quenched with sat. aq. NaHCO3, extracted with EtOAc (1 L × 3). Combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel (100% petroleum ether) to afford the title compound (44.0 g, 44%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.74 (d, J = 2.0 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 2.0 Hz, 1H). [0491] Step 3: Preparation of 4-Bromo-7-chloro-2,3-dihydrobenzofuran [0492] A mixture of Rh/C (10.0 g, 95.0 mmol) and 4-bromo-7-chlorobenzofuran (44.0 g, 190 mmol) in EtOH (440 mL) was stirred at room temperature for 2 hours under an atmosphere of H ₂ (15 psi). The reaction was filtered and the filtrate was concentrated. The residue was purified by chromatography on silica gel (100% petroleum ether) to afford the title compound (33.0 g, 74%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.01 (d, J = 8.8 Hz, 1H), 6.93 (d, J = 8.8 Hz, 1H), 4.72 (t, J = 8.8 Hz, 2H), 3.30 (t, J = 8.8 Hz, 2H). [0493] Step 4: Preparation of 4-bromo-7-chloro-5-nitro-2,3-dihydrobenzofuran [0494] To the mixture of 4-bromo-7-chloro-2,3-dihydrobenzofuran (30.0 g, 128.5 mmol) in TFA (300 mL) was added HNO ₃ (11.4 mL, 257.0 mmol) at 0°C dropwise slowly. The reaction mixture was then stirred for 2 hours. The reaction mixture was quenched with sat. aq. NaOH, and the mixture was extracted with EtOAc (1 L × 3), the combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (27.0 g, 76%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.97 (s, 1H), 4.88 (t, J = 8.8 Hz, 2H), 3.42 (t, J = 8.8 Hz, 2H). [0495] Step 5: Preparation of methyl 7-chloro-5-nitro-2,3-dihydrobenzofuran-4- carboxylate [0496] A solution of 4-bromo-7-chloro-5-nitro-2,3-dihydrobenzofuran (1.0 g, 3.59 mmol), Pd(OAc) ₂ (80 mg, 0.36 mmol), Na ₂ CO ₃ (1.14 g, 10.77 mmol) and Xantphos (208 mg, 0.36 mmol) in DMF (5 mL) and MeOH (5 mL) was stirred at 80°C for 16 hours under an atmosphere of CO (15 psi). The reaction solution was quenched with water (200 mL), extracted with EtOAc (200 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (0 - 20% ethyl acetate in petroleum ether) to afford the title compound (300 mg, 32%) as a brown solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.02 (s, 1H), 4.88 (t, J = 8.8 Hz, 2H), 3.94 (s, 3H), 3.42 (t, J = 8.8 Hz, 2H). [0497] Step 6: Preparation of methyl 5-amino-7-chloro-2,3-dihydrobenzofuran-4- carboxylate [0498] To a solution of methyl 7-chloro-5-nitro-2,3-dihydrobenzofuran-4-carboxylate (300 mg, 1.16 mmol) in HOAc (5 mL) was added Fe powder (326 mg, 5.82 mmol). The reaction was stirred at 50 °C for 1 hour. The reaction mixture was diluted with water (30 mL) and the pH adjusted to 8 with 2M NaOH solution. The mixture was extracted with EtOAc (50 mL × 3), the combined organic layers were dried over Na2SO4 and concentrated under vacuum. The residue was purified by chromatography on silica gel (0 - 50% EtOAc in petroleum ether) to afford the title compound (196 mg, 74%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 6.55 (s, 1H), 5.39 (s, 2H), 4.59 (t, J = 8.8 Hz, 2H), 3.87 (s, 3H), 3.53 (t, J = 8.8 Hz, 2H). EXAMPLE 1 [0499] Preparation of (E)-3-cyano-N-(5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0500] The reaction scheme was as follows: [0501] Step 1: (E)-methyl 4-amino-4-oxobut-2-enoate [0502] A mixture of (2E)-4-methoxy-4-oxo-2-butenoic acid (20.0 g, 153 mmol) and thionylchloride (25.0 mL, 344 mmol) was stirred at 80°C under a nitrogen atmosphere for 48 hours at which point the reaction mixture was concentrated. The residue was diluted with toluene (100 mL) and concentrated to afford methyl (E)-methyl 4-chloro-4-oxobut-2-enoate (20.0 g, 87%) as a brown oil which was used for the next step directly without further purification. Ammonia (15.0 g, 21 mmol) was condensed into THF (300 mL) at -78°C at which point the reaction was warmed to 0°C. Then (E)-methyl 4-chloro-4-oxobut-2-enoate (20.0 g, 134 mmol) in THF (30 mL) was added dropwise while maintaining a reaction temperature of 0°C. Upon completion of the addition the reaction was stirred at room temperature for 16 hours. The reaction mixture was concentrated and the crude material was diluted in EtOAc (300 mL), filtered and concentrated to afford the title compound (5.00 g, 29%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 7.91 (s, 1H), 7.52 (s, 1H), 6.97 (d, J = 15.6 Hz, 1H), 6.57 (d, J = 15.6 Hz, 1H), 3.72 (s, 3H). [0503] Step 2: (E)-methyl 3-cyanoacrylate [0504] (E)-methyl 4-amino-4-oxobut-2-enoate (4.00 g, 31.0 mmol) was dissolved in pyridine (34.0 mL) at 0°C under nitrogen atmosphere then phosphorus oxychloride (4.40 mL, 47.2 mmol) was added slowly. After 1 hour the mixture was warmed to room temperature for an additional 1.5 hours. The reaction mixture was quenched with ice water (100 mL) and extracted with DCM (100 mL × 3). The organic layer was washed with HCl (2.0 M, 100 mL), then saturate aqueous NaHCO3 (50 mL) and then the organic phase was concentrated to afford the title compound (1.50 g, 44%) as a yellow oil.1H NMR (400 MHz, CDCl3): δ 6.72 (d, J = 16.4 Hz, 1H), 6.51 (d, J = 16.4 Hz, 1H), 3.85 (s, 3H). [0505] Step 3: (E)-3-cyanoacrylic acid [0506] Diethylzinc To a solution of methyl (E)-3-cyanoprop-2-enoate (500 mg, 4.5 mmol) in water (1.0 mL) and THF (2.0 mL) was added lithium hydroxide monohydrate (800 mg, 19.0 mmol). The reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted in water (40 mL), and adjusted to pH 6.0 with HCl (1.0 M). The solution was extracted with EtOAc (40 mL × 2). The combined organic layers were dried over Na2SO4 and concentrated to afford the title compound (270 mg, 62%) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 6.94 (d, J = 16.4 Hz, 1H), 6.73 - 6.61 (m, 1H). [0507] Step 4: (E)-3-Cyano-N-(5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0508] To a mixture of (E)-3-cyanoprop-2-enoic acid (130 mg, 1.33 mmol), HATU (760 mg, 2 mmol) and 5-methoxy-4-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl)viny l)pyridin-2- amine (Intermediate D, 200 mg, 0.67 mmol) in DMF (10 mL) was added DIPEA (1.0 mL, 5.94 mmol). The reaction was stirred at 0°C for 2 hours. The reaction mixture was diluted in water (40 mL), extracted with EtOAc (40 mL × 2). The combined organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by prep-TLC (50% EtOAc in petroleum ether) and further purified by SFC (daicel chiralcel OD (250mm*30mm,10um), Neu-EtOH, 20% - 20%) and prep-TLC (50% EtOAc in petroleum ether) to afford the title compound (6.29 mg, 2%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.69 (s, 1H), 8.33 (s, 1H), 7.90 (s, 1H), 6.90 (d, J = 16.0 Hz, 1H), 6.71 - 6.57 (m, 2H), 6.48 (dd, J = 16.0, 6.8 Hz, 1H), 3.94 (s, 3H), 2.25 - 2.14 (m, 1H), 2.06 - 1.95 (m, 5H), 1.46 - 1.35 (m, 2H), 1.30 - 1.23 (m, 2H). LCMS (ESI): m/z 380.2 (M+H) ⁺ . EXAMPLE 2 [0509] Preparation of N-(6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0510] To a mixture of 6-methoxy-5-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl)viny l) pyridin-3-amine (Intermediate F, 200 mg, 0.670 mmol) and DIPEA (0.500 ml, 3.00 mmol) in dichloromethane (2.0 ml) was added acryloyl chloride (0.120 ml, 1.47 mmol) at 0°C. And the reaction was stirred at 0°C for 2 hours. The reaction mixture was diluted with water (40 mL), and extracted with DCM (40 mL × 2). The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by prep-TLC (25% EtOAc in petroleum ether) to afford the title compound (58.37 mg, 23%) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.18 (s, 1H), 8.27 (dd, J = 9.6, 2.4 Hz, 1H), 8.10 (d, J = 2.4 Hz, 1H), 6.53 - 6.35 (m, 2H), 6.31 - 6.17 (m, 2H), 5.76 (dd, J = 12.0, 2.0 Hz, 1H), 3.86 (s, 3H), 2.21 - 2.14 (m, 2H), 1.90 – 1.83 (m, 4H), 1.32 - 1.20 (m, 4H). LCMS (ESI): m/z 355.2 (M+H) ⁺ . EXAMPLE 3 [0511] Preparation of N-(6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)but-2-ynamide [0512] To the mixture of but-2-ynoic acid (70.0 mg, 0.83 mmol) and N- methylmorpholine (152 mg, 1.50 mmol) in dichloromethane (2.0 mL) was added isobutyl chloroformate (109 mg, 0.80 mmol) dropwise at 0°C. The resulting mixture was stirred at 0°C for 15 minutes. The reaction mixture was added to a mixture of 6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-amine (Intermediate F, 100 mg, 0.33 mmol), pyridine (1.0 mL) and 4-dimethylaminopyridine (1.00 mg, 0.01 mmol). The reaction was stirred at room temperature for 2 hours then it was quenched with H ₂ O (20 mL). The resulting solution was extracted with EtOAc (50 mL × 2), washed with H2O (100 mL × 2). The organic layers were dried over Na2SO4 and concentrated. The residual was purified by prep-TLC (20% EtOAc in petroleum ether) to afford the title compound (44.11 mg, 35%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 2.4 Hz, 1H), 7.97 (d, J = 2.4 Hz, 1H), 7.38 (s, 1H), 6.52 (d, J = 16.0 Hz, 1H), 6.22 (dd, J = 16.0, 6.8 Hz, 1H), 3.95 (s, 3H), 2.20 - 2.10 (m, 1H), 2.05 - 1.94 (m, 8H), 1.45 - 1.33 (m, 2H), 1.28 - 1.16 (m, 2H); LCMS (ESI): m/z 367.1 (M+H) ⁺ . EXAMPLE 4 [0513] Preparation of (E)-N-(5-(2-(4,4-Difluorocyclohexyl)vinyl)-6-methoxypyridin- 3- yl)acrylamide [0514] The title compound (97.9 mg, 41%) was furnished as a white solid. It was prepared from E)-5-(2-(4,4-difluorocyclohexyl)vinyl)-6-methoxypyridin-3-am ine (200 mg, 0.75 mmol) and acryloyl chloride (60.29 uL, 0.75 mmol) following the procedure outlined for Example 2. It was purified by prep-HPLC (Boston Green ODS 150*30mm*5um, water (0.2%FA)-ACN, 60-90%) to afford the title compound (97.9 mg, 41%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 10.18 (s, 1H), 8.28 (d, J = 2.4 Hz, 1H), 8.09 (d, J = 2.4 Hz, 1H), 6.52 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 10.0 Hz, 1H), 6.31 - 6.22 (m, 2H), 5.77 (dd, J = 12.0, 1.6 Hz, 1H), 3.87 (s, 3H), 2.37 - 2.30 (m, 1H), 2.09 - 1.99 (m, 2H), 1.98 - 1.90 (m, 1H), 1.88 - 1.80 (m, 3H), 1.49 - 1.37 (m, 2H). LCMS (ESI): m/z 323.2 (M+H) ⁺ . EXAMPLE 5 [0515] Preparation of N-(6-Methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridazin-3-yl)acrylamide

(trifluoromethyl)cyclohexyl)vinyl)pyridazine [0517] The title compound (2.70 g, 83%) was furnished as a white solid. It was prepared from diethyl ((6-chloro-3-methoxypyridazin-4-yl)methyl)phosphonate (3.00 g, 10.18 mmol) and Trans-4-(trifluoromethyl)cyclohexanecarbaldehyde (Intermediate A, 3.70 g, 20.36 mmol) following the procedure outlined for Intermediate C, Step 6. ¹ H NMR (400 MHz, CDCl3): δ 7.34 (s, 1H), 6.51 (dd, J = 16.0, 6.8 Hz, 1H), 6.43 (d, J = 16.0 Hz, 1H), 4.15 (s, 3H), 2.28 - 2.16 (m, 1H), 2.06 - 1.96 (m, 5H), 1.43 - 1.37 (m, 2H), 1.28 - 1.22 (m, 2H). [0518] Step 2: 6-Methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridazin-3-amine [0519] The title compound (300 mg, 32%) was furnished as a yellow solid. It was prepared from 6-chloro-3-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridazine (1.00 g, 3.12 mmol) following the procedure outlined for Intermediate D. LCMS (ESI): m/z 302.2 (M+H) ⁺ . [0520] Step 3: N-Acryloyl-N-(6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridazin-3-yl)acrylamide [0521] To a mixture of 6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridazin-3-amine (200 mg, 0.660 mmol) in DCM (6.0 mL) was added DIPEA (0.700 mL, 3.87 mmol) and acryloyl chloride (0.120 mL, 1.32 mmol) at 0°C. The reaction was stirred at 0°C under N2 (15 psi) for 30 minutes. The solvent was removed under reduced pressure to afford the crude compound (270 mg) as a brown solid which was used without further purification. LCMS (ESI): m/z 410.2 (M+H) ⁺ . [0522] Step 4: N-(6-Methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridazin-3-yl)acrylamide [0523] To a solution of N-acryloyl-N-(6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridazin-3-yl)acrylamide (270 mg, 0.66 mmol) in THF (3.0 mL) was added a solution of sodium hydroxide (2.0 M, 3.0 mL, 6.0 mmol). The reaction was stirred at 0°C for 30 minutes. The reaction mixture was diluted by water (10 mL), extracted with EtOAc (10 mL × 2). The organic layers were combined, dried over Na ₂ SO ₄ and concentrated. The resulting residue was purified by prep-HPLC (acetonitrile 45-75/0.2% FA in water, Xtimate C18150*40mm*10um) to afford the title compound (28.2 mg, 11%) as a white solid. ¹ H NMR (400 MHz,CDCl3): δ 10.23 (s, 1H), 8.65 (s, 1H), 6.90 (dd, J = 16.0, 6.8 Hz, 1H), 6.62 (dd, J = 16.0, 6.8 Hz, 1H), 6.57 - 6.46 (m, 2H), 5.83 (d, J = 10.8 Hz, 1H), 4.14 (s, 3H), 2.30 - 2.14 (m, 1H), 2.08 - 1.94 (m, 5H), 1.47 - 1.36 (m, 2H), 1.30 - 1.20 (m, 2H). LCMS (ESI): m/z 356.2 (M+H) ⁺ . EXAMPLE 6 [0524] Preparation of N-(5-Methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0525] Step 1: N-Acryloyl-N-(5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0526] The title compound (81.0 mg) was furnished as a yellow oil. It was prepared from 5-methoxy-4-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl)viny l)pyridin-2-amine (Intermediate D, 60.0 mg, 0.20 mmol) following the procedure outlined for Example 5, Step 3. LCMS (ESI): m/z 409.2 (M+H) ⁺ . [0527] Step 2: N-(5-Methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0528] The title compound (9.82 mg, 14%) was furnished as a white solid. It was prepared from N-acryloyl-N-(5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide (81 mg, 0.20 mmol) following the procedure outlined for Example 5, Step 4. ¹ H NMR (400 MHz, CD3OD): δ 8.21 (s, 1H), 7.98 (s, 1H), 6.68 (d, J = 16.0 Hz ¹ H), 6.54 - 6.44 (m, 2H), 6.40 (dd, J = 16.0, 2.0 Hz, 1H), 5.79 (dd, J = 10.0, 2.0 Hz, 1H), 3.92 (s, 3H), 2.22 - 2.08 (m, 2H), 2.06 - 1.91 (m, 4H), 1.48 - 1.26 (m, 4H). LCMS (ESI): m/z 355.2 (M+H) ⁺ . EXAMPLE 7 [0529] Preparation of (E)-N-(4-(2-(4,4-difluorocyclohexyl)vinyl)-5-methoxypyridin- 2- yl)acrylamide [0530] The reaction scheme was as follows: [0531] Step 1: (E)-N-Acryloyl-N-(4-(2-(4,4-difluorocyclohexyl)vinyl)-5- methoxypyridin-2-yl)acrylamide [0532] The title compound (210 mg) was furnished as a yellow oil. It was prepared from 4-[(E)-2-(4,4-difluorocyclohexyl)vinyl]-5-methoxy-pyridin-2- amine (Intermediate E, 150 mg, 0.560 mmol) following the procedure outlined for Example 5, Step 3. LCMS (ESI): m/z 377.2 (M+H) ⁺ . [0533] Step 2: (E)-N-(4-(2-(4,4-Difluorocyclohexyl)vinyl)-5-methoxypyridin- 2- yl)acrylamide [0534] The title compound (51.2 mg, 40%) was furnished as a white solid. It was prepared from (E)-N-Acryloyl-N-(4-(2-(4,4-difluorocyclohexyl)vinyl)-5-meth oxypyridin-2- yl)acrylamide (210 mg, 0.560 mmol) following the procedure outlined for Example 5, Step 4. It was purified by prep-TLC (50% EtOAc in petroleum ether) and further purified by SFC (daicel chiralpak AD-H (250mm*30mm,5um), 0.1% NH ₃ H ₂ O-EtOH, 30% - 30%). ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.39 (s, 1H), 8.05 (s, 1H), 7.88 (s, 1H), 6.69 (d, J = 16.4 Hz, 1H), 6.60 - 6.41 (m, 2H), 6.26 (dd, J = 16.8, 10.0 Hz, 1H), 5.81 (d, J = 10.0 Hz, 1H), 3.92 (s, 3H), 2.30 - 2.29 (m, 1H), 2.21 - 2.09 (m, 2H), 1.91 - 1.86 (m, 2H), 1.78 - 1.70 (m, 2H), 1.67 - 1.55 (m, 2H). LCMS (ESI): m/z 323.2 (M+H) ⁺ . EXAMPLE 8 [0535] Preparation of N-(5-methoxy-6-methyl-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0536] The reaction scheme was as follows:

[0537] Step 1: 6-Chloro-3-methoxy-2-methyl-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl) vinyl)pyridine [0538] To a mixture of 2-chloro-5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridine (Intermediate C, 300 mg, 0.94 mmol) in THF (5 mL) was added n-BuLi (2.5 M in THF, 0.52 mL, 1.03 mmol) dropwise at -78°C. The mixture was stirred at -78°C for 30 minutes. Then MeI (266 mg, 1.88 mmol) was added into the mixture. The mixture was warmed to room temperature and stirred for 1 hour. The reaction mixture was diluted with water (50 mL × 2). The resulting solution was extracted with EtOAc (50 mL × 2) and the organic layers were combined. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by prep-TLC (30% EtOAc in petroleum ether) to afford the title compound (220 mg, 70%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.20 (s, 1H), 6.55 (d, J = 16.4 Hz, 1H), 6.36 (dd, J = 16.4, 7.2 Hz, 1H), 3.71 (s, 3H), 2.48 (s, 3H), 2.25 - 2.21 (m, 1H), 2.08 - 1.93 (m, 5H), 1.50 - 1.35 (m, 2H), 1.30 - 1.19 (m, 2H). [0539] Step 2: 5-Methoxy-6-methyl-4-((E)-2-(trans-4-(trifluoromethyl)cycloh exyl)vinyl) pyridin-2-amine [0540] The title compound (75 mg, 80%) was furnished as a white solid. It was prepared from 6-chloro-3-methoxy-2-methyl-4-((E)-2-(-4-(trifluoromethyl) cyclohexyl)vinyl)pyridine (100 mg, 0.30 mmol) following the procedure outlined for Intermediate D. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.53 (d, J = 16.0 Hz, 1H), 6.39 (s, 1H), 6.26 (dd, J = 16.0, 7.2 Hz, 1H), 4.16 (s, 2H), 3.64 (s, 3H), 2.37 (s, 3H), 2.26 - 2.13 (m, 1H), 2.07 - 1.93 (m, 5H), 1.47 - 1.34 (m, 2H), 1.29 - 1.17 (m, 2H). [0541] Step 3: 5-Methoxy-6-methyl-4-((E)-2-(trans-4-(trifluoromethyl)cycloh exyl)vinyl) pyridin-2-amine [0542] The title compound (25.7 mg, 30%) was furnished as a white solid. It was prepared from 5-methoxy-6-methyl-4-((E)-2-(trans-4-(trifluoromethyl)cycloh exyl)vinyl) pyridin-2-amine (70 mg, 0.22 mmol) in DCM (4.4 mL) at 0°C was added dropwise acryloyl chloride (0.015 mL, 0.28 mmol). The reaction mixture was stirred at 0°C for 4 hours. The mixture was diluted with water (30 mL) and the resultant mixture was extracted with DCM (30 mL × 3). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by prep-TLC (10% EtOAc in petroleum ether) to afford the title compound (12.29 mg, 27%) as a white solid. It was then purified by prep-HPLC (Xtimate C18 150*40mm*10um; water (0.2% HCO ₂ H)-ACN; 48/78). ¹ H NMR (400MHz, CDCl ₃ ): δ 8.25 (s, 1H), 8.01 (s, 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.52 - 6.42 (m, 2H), 6.24 (dd, J = 16.0, 10.0 Hz, 1H), 5.81 (d, J = 10.0 Hz, 1H), 3.71 (s, 3H), 2.43 (s, 3H), 2.28 - 2.14 (m, 1H), 2.07 - 1.93 (m, 5H), 1.48 - 1.35 (m, 2H), 1.31 - 1.18 (m, 2H). LCMS (ESI): m/z 369.2 (M+H) ⁺ . EXAMPLE 9 [0543] Preparation of N-(6-methoxy-5-(((trans-4- (trifluoromethyl)cyclohexyl)oxy)methyl)pyridin-3-yl)acrylami de [0544] The overall reaction scheme was as follows:

[0545] Step 1: 5-Bromo-2-methoxy-3-(((trans-4 (trifluoromethyl)cyclohexyl)oxy)methyl)pyridine [0546] To a stirred solution of trans-4-(trifluoromethyl)cyclohexanol (300 mg, 1.78 mmol) in THF (8.0 mL) was added NaH (60% in mineral oil, 43 mg, 1.78 mmol) at 0°C. After 10 minutes, 5-bromo-3-(bromomethyl)-2-methoxypyridine (550 mg, 1.96 mmol) was added into the reaction and the mixture was stirred at 60°C for 3 hours. The mixture was quenched with H ₂ O (10 ml), extracted with EtOAc (20 mL × 2). The organic layers were combined, washed with brine (20 mL). The reaction mixture was dried over Na2SO4 and concentrated. The crude was purified by column chromatography on silica gel (0 - 2.5% EtOAc in petroleum ether) to afford the title compound (360 mg, 45%) as a colorless oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.10 (d, J = 2.4 Hz, 1H), 7.78 (d, J = 2.4 Hz, 1H), 4.50 (s, 2H), 3.93 (s, 3H), 3.39 - 3.31 (m, 1H), 2.24 - 2.21 (m, 2H), 2.08 - 1.99 (m, 3H), 1.40 - 1.29 (m, 4H). [0547] Step 2: 6-Methoxy-5-(((trans-4-(trifluoromethyl)cyclohexyl)oxy)methy l)pyridin- 3-amine [0548] The title compound (150 mg, 62 %) was furnished as a brown solid. It was prepared from 5-bromo-2-methoxy-3-(((trans-4(trifluoromethyl)cyclohexyl)ox y)methyl)pyridine (360 mg, 0.80 mmol) following the procedure outlined for Intermediate D. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.38 (d, J = 2.4 Hz, 1H), 7.05 (d, J = 2.4 Hz, 1H), 4.75 (s, 2H), 4.38 (s, 2H), 3.73 (s, 3H), 3.33 - 3.30 (m, 1H), 2.35 - 2.19 (m, 1H), 2.13 - 2.10 (m, 2H), 1.95 - 1.81 (m, 2H), 1.35 - 1.19 (m, 5H). [0549] Step 3: N-(6-Methoxy-5-(((trans-4- (trifluoromethyl)cyclohexyl)oxy)methyl)pyridin-3-yl)acrylami de [0550] The title compound (113 mg, 64%) was furnished as a white solid. It was prepared from 6-methoxy-5-(((trans-4-(trifluoromethyl)cyclohexyl)oxy)methy l)pyridin-3-amine (150 mg, 0.49 mmol) and acryloyl chloride (0.050 mL, 0.59 mmol) following the procedure outlined for Example 2. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.17 (s, 1H), 8.40 (d, J = 2.0 Hz, 1H), 7.95 (d, J = 2.0 Hz, 1H), 6.40 (dd, J = 16.8, 10.0 Hz, 1H), 6.25 (d, J = 16.8, 2.0 Hz, 1H), 5.76 (dd, J = 10.0, 2.0 Hz, 1H), 4.48 (s, 2H), 3.85 (s, 3H), 3.33 - 3.30 (m, 1H), 2.29 - 2.26 (m, 1H), 2.15 - 2.13 (m, 2H), 1.89 - 1.87 (m, 2H), 1.34 - 1.20 (m, 4H). LCMS (ESI): m/z 359.1 (M+H) ⁺ .

EXAMPLE 10 [0551] Preparation of N-(5-(((4,4-difluorocyclohexyl)oxy)methyl)-6-methoxypyridin- 3- yl)acrylamide [0552] The overall reaction scheme was as follows: [0553] Step 1: 5-Bromo-3-(((4,4-difluorocyclohexyl)oxy)methyl)-2-methoxypyr idine [0554] The title compound (775 mg, 79%) was furnished as a colorless oil. It was prepared from 4,4-difluorocyclohexanol (400 mg, 2.94 mmol) and 5-bromo-3-(bromomethyl)-2- methoxypyridine (908 mg, 3.23 mmol) following the procedure outlined for Example 9, Step 1. ¹ H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 2.4 Hz, 1H), 7.77 (d, J = 2.4 Hz, 1H), 4.45 (s, 2H), 3.93 (s, 3H), 3.65 - 3.62 (m, 1H), 2.15 - 2.05 (m, 2H), 1.95 - 1.82 (m, 6H). [0555] Step 2: 5-(((4,4-Difluorocyclohexyl)oxy)methyl)-6-methoxypyridin-3-a mine [0556] The title compound (340 mg, 70%) was furnished as a white solid. It was prepared from 5-bromo-3-(((4,4-difluorocyclohexyl)oxy)methyl)-2-methoxypyr idine (600 mg, 1.78 mmol) following the procedure outlined for Intermediate D. ¹ H NMR (400 MHz, CDCl3): δ 7.57 (d, J = 2.8 Hz, 1H), 7.17 (d, J = 2.8 Hz, 1H), 4.45 (s, 2H), 3.88 (s, 3H), 3.68 - 3.58 (m, 1H), 3.39 (s, 2H), 2.21 - 2.04 (m, 2H), 1.99 - 1.82 (m, 6H). [0557] Step 3: N-(5-(((4,4-difluorocyclohexyl)oxy)methyl)-6-methoxypyridin- 3- yl)acrylamide [0558] The title compound (135 mg, 75%) was furnished as a white solid. It was prepared from 5-(((4,4-difluorocyclohexyl)oxy)methyl)-6-methoxypyridin-3-a mine (150.0 mg, 0.550 mmol) and acryloyl chloride (0.05 mL, 0.660 mmol) following the procedure outlined for Example 2. It was purified by prep-HPLC (Xtimate C18150*40mm*10um, water (0.2%FA)- ACN, 35-65%). ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.19 (s, 1H), 8.43 (d, J = 2.4 Hz, 1H), 7.98 (d, J = 2.4 Hz, 1H), 6.41 (dd, J = 16.8, 10.0 Hz, 1H), 6.25 (dd, J = 16.8, 2.0 Hz, 1H), 5.76 (dd, J = 10.0, 2.0 Hz, 1H), 4.46 (s, 2H), 3.85 (s, 3H), 3.65 - 3.63 (m, 1H), 2.07 - 1.74 (m, 8H). LCMS (ESI): m/z 327.1 (M+H) ⁺ . EXAMPLE 11 [0559] Preparation of N-(6-Methoxy-5-((spiro[2.3]hexan-5-yloxy)methyl)pyridin-3- yl)acrylamide [0560] The overall reaction scheme was as follows: [0562] To a solution of spiro[2.3]hexan-5-one (500 mg, 5.2 mmol) in MeOH (2.5 ml) and THF (5.0 ml) was added NaBH ₄ (393 mg, 10.4 mmol) at 0°C. Then the result mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched with water (100 mL) and extracted with EtOAc (50 mL × 2). The combined organic layers were dried with Na ₂ SO ₄ and concentrated to afford the title compound (490 mg, 96%) as a colorless oil. ¹ H NMR (400 MHz, CDCl3): δ 4.57 - 4.50 (m, 1H), 2.29 - 2.17 (m, 4H), 0.45 - 0.36 (m, 4H). [0563] Step 2: 5-Bromo-2-methoxy-3-((spiro[2.3]hexan-5-yloxy)methyl)pyridin e [0564] The title compound (380 mg, 50%) was furnished as a colorless oil. It was prepared from spiro[2.3]hexan-5-ol (250 mg, 2.55 mmol) and 5-bromo-3-(bromomethyl)-2 methoxypyridine (787 mg, 2.80 mmol) following the procedure outlined for Example 9, Step 1. ¹ H NMR (400 MHz, CD3OD): δ 8.11 (d, J = 2.4 Hz, 1H), 7.81 (d, J = 2.4 Hz, 1H), 4.38 (s, 2H), 4.36 - 4.31 (m, 1H), 3.93 (s, 3H), 2.33 - 2.26 (m, 2H), 2.24 - 2.17 (m, 2H), 0.50 - 0.44 (m, 2H), 0.43 - 0.38 (m, 2H). [0565] Step 3: 6-Methoxy-5-((spiro[2.3]hexan-5-yloxy)methyl)pyridin-3-amine [0566] The title compound (220 mg, 73%) was furnished as a brown oil. It was prepared from 5-bromo-2-methoxy-3-((spiro[2.3]hexan-5-yloxy)methyl)pyridin e (380 mg, 1.27 mmol) following the procedure outlined for Intermediate D. ¹ H NMR (400 MHz, CD3OD): δ 7.54 (d, J = 2.4 Hz, 1H), 7.25 (d, J = 2.4 Hz, 1H), 4.35 (s, 2H), 4.32 - 4.26 (m, 1H), 3.85 (s, 3H), 2.31 - 2.24 (m, 2H), 2.22 - 2.14 (m, 2H), 0.49 - 0.44 (m, 2H), 0.42 - 0.37 (m, 2H). LCMS (ESI): m/z 235.0 (M+H) ⁺ . [0567] Step 4: N-(6-Methoxy-5-((spiro[2.3]hexan-5-yloxy)methyl)pyridin-3- yl)acrylamide [0568] The title compound (88.0 mg, 68%) was furnished as a white solid. It was prepared from 6-methoxy-5-((spiro[2.3]hexan-5-yloxy)methyl)pyridin-3-amine (100 mg, 0.43 mmol), and acryloyl chloride (0.05 mL, 0.64 mmol) following the procedure outlined for Example 2. ¹ H NMR (400 MHz, DMSO-d6): δ 10.20 (s, 1H), 8.43 (d, J = 2.4 Hz, 1H), 7.97 (d, J = 2.4 Hz, 1H), 6.41 (dd, J = 16.8, 10.0 Hz, 1H), 6.26 (dd, J = 16.8, 2.0, 1H), 5.77 (dd, J = 10.0, 2.0 Hz, 1H), 4.34 (s, 2H), 4.32 - 4.26 (m, 1H), 3.86 (s, 3H), 2.24 - 2.17 (m, 4H), 0.47 - 0.42 (m, 2H), 0.41 - 0.35 (m, 2H). LCMS (ESI): m/z 289.2 (M+H) ⁺ . EXAMPLE 12 [0569] Preparation of N-6-Cyclopropyl-5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0570] The overall reactions scheme was as follows: [0571] Step 1: 6-Chloro-2-iodo-3-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridine [0572] To a mixture of 2-chloro-5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridine (Intermediate C, 500 mg, 1.56 mmol) in THF (10 mL) was added n-BuLi (2.5M in THF, 0.80 mL, 2.0 mmol) at -78°C. The reaction was stirred at -78°C under N ₂ for 30 minutes. I ₂ (400 mg, 1.58 mmol) in THF (5.0 mL) was added to the reaction at -78°C. The reaction was stirred at -78°C under N ₂ for 2 hours. The reaction was quenched with water (100 mL). The solution was extracted with EtOAc (200 mL × 3). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (500 mg, 72%) as a yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.69 (s, 1H), 6.75 (dd, J = 16.0, 6.8 Hz, 1H), 6.46 (d, J = 16.0 Hz, 1H), 3.72 (s, 3H), 2.31 - 2.16 (m, 2H), 1.98 - 1.80 (m, 4H), 1.40 - 1.20 (m, 4H). [0573] Step 2: 6-Chloro-2-cyclopropyl-3-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridine [0574] To a solution of 6-chloro-2-iodo-3-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridine (500 mg, 1.12 mmol) in toluene (12 mL) were added Pd(OAc) ₂ (25.0 mg, 0.11 mmol), K ₃ PO ₄ (715 mg, 3.37 mmol), Cy ₃ P (32.0 mg, 0.11 mmol) and cyclopropylboronicacid (200 mg, 2.33 mmol). Then the reaction mixture was placed under nitrogen atmosphere and stirred at 100°C for 16 hours. The reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (350 mg, 86%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.07 (s, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.34 (dd, J = 16.0, 6.8 Hz, 1H), 3.78 (s, 3H), 2.28 - 2.25 (m, 1H), 2.16 - 2.08 (m, 1H), 1.97 - 1.86 (m, 4H), 1.42 - 1.27 (m, 3H), 1.215 - 1.20 (m, 2H), 1.05 - 0.98 (m, 2H), 0.95 - 0.88 (m, 2H). [0575] Step 3: 6-Cyclopropyl-5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-amine [0576] The title compound (40.0 mg, 12%) was furnished as a brown solid. It was prepared from 6-chloro-2-cyclopropyl-3-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridine (350 mg, 0.970 mmol) following the procedure outlined for Intermediate D. ¹ H NMR (400 MHz, CDCl3): δ 6.55 (d, J = 16.0 Hz, 1H), 6.29 (s, 1H), 6.25 (dd, J = 16.0, 6.8 Hz, 1H), 4.06 (s, 2H), 3.72 (s, 3H), 2.34 - 2.25 (m, 1H), 2.18 - 2.16 (m, 1H), 2.07 - 1.95 (m, 5H), 1.47 - 1.35 (m, 2H), 1.25 - 1.21 (m, 2H), 0.99 - 0.98 (m, 2H), 0.89 - 0.86 (m, 2H). [0577] Step 4: N-(6-Cyclopropyl-5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0578] To a solution of compound 6-cyclopropyl-5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-amine (40 mg, 0.12 mmol) in DCM (3 mL) at 0°C was added dropwise acryloyl chloride (0.010 mL, 0.15 mmol). The reaction mixture was stirred at 0°C for 4 hours. The mixture was diluted with water (30 mL) and the resultant mixture was extracted with DCM (30 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by prep-TLC (10% EtOAc in petroleum ether) to afford the title compound (12.29 mg, 27%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.13 (s, 1H), 7.66 (s, 1H), 6.63 (d, J = 16.0 Hz, 1H), 6.51 - 6.37 (m, 2H), 6.32 - 6.16 (m, 1H), 5.80 (d, J = 11.6 Hz, 1H), 3.78 (s, 3H), 2.40 - 2.31 (m, 1H), 2.25 - 2.15 (m, 1H), 2.07 - 1.92 (m, 5H), 1.47 - 1.36 (m, 2H), 1.27 - 1.23 (m, 2H), 1.00 - 0.93 (m, 4H). LCMS (ESI): m/z 395.2 (M+H) ⁺ . EXAMPLE 13 [0579] Preparation of N-(2-Cyano-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0580] The overall reaction scheme was as follows: [0581] Step 1: 5-Bromo-2-methoxy-3-methylpyridine 1-oxide [0582] To the mixture of 5-bromo-2-methoxy-3-methylpyridine (14.5 g, 71.76 mmol) in DCM (145 mL) was added 3-chlorobenzoperoxoic acid (58.3 g, 287.06 mmol) in portions. The reaction was stirred at room temperature for 16 hours. The reaction solution was filtered to remove the solid. The filtrate was filtered with silica gel (30 g) to absorb the crude compound with the silica gel. The residue was purified by column chromatography on silica gel (0 - 4% MeOH in DCM) to afford the title compound (2.20 g, 14%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.19 (s, 1H), 7.22 (s, 1H), 4.14 (s, 3H), 2.28 (s, 3H); LCMS (ESI): m/z 217.9 (M+H) ⁺ . [0583] Step 2: 3-Bromo-6-methoxy-5-methylpicolinonitrile [0584] To a solution of 5-bromo-2-methoxy-3-methylpyridine 1-oxide (2.00 g, 9.17 mmol) in acetonitrile (20 mL) was added trimethylsilanecarbonitrile (3.60 g, 36.69 mmol) and triethylamine (3.81 mL, 27.52 mmol). The result solution was stirred at 80°C for 16 hours. Then the mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0 - 10 % EtOAc in petroleum ether) to afford the title compound (1.18 g, 56%) as a white solid. LCMS (ESI): m/z 227.8 (M+H) ⁺ . [0585] Step 3: 3-Bromo-5-(bromomethyl)-6-methoxypicolinonitrile [0586] To a mixture of 3-bromo-6-methoxy-5-methylpicolinonitrile (1.18 g, 5.20 mmol) in CCl4 (20 mL) was added (E)-2,2'-(diazene-1,2-diyl)bis(2-methylpropanenitrile) (9 mg, 0.050 mmol) and NBS (924 mg, 5.20 mmol). The reaction was stirred at 80°C for 2 hours. Water (50 mL) was added into the solution and the mixture was extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine (30 mL), dried with Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 2% EtOAc in petroleum ether) to afford the title compound (820 mg, 51%) as a white solid. LCMS (ESI): m/z 306.8 (M+H) ⁺ . [0587] Step 4: Diethyl ((5-bromo-6-cyano-2-methoxypyridin-3-yl)methyl)phosphonate [0588] A mixture of 3-bromo-5-(bromomethyl)-6-methoxypicolinonitrile (820 mg, 2.26 mmol) and triethyl phosphite (1.55 mL, 21.20 mmol) were stirred at 130°C for 3 hours under reflux. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (0 - 30% EtOAc in petroleum ether) to afford the title compound (1.35 g, 70% purity). LCMS (ESI): m/z 362.9 (M+H) ⁺ . [0589] Step 5: 3-Bromo-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)picolinonitrile [0590] To a solution of diethyl ((5-bromo-6-cyano-2-methoxypyridin-3- yl)methyl)phosphonate (1.35 g, 3.72 mmol) in toluene (10 mL) was added sodium tert-pentoxide (0.54 g, 4.82 mmol) at 0°C. The resultant mixture was stirred for 20 minutes at 0°C, at which point a solution of trans-4-(trifluoromethyl)cyclohexanecarbaldehyde (1.35 g, 7.44 mmol) in THF (10 mL) was added dropwise at 0°C. The reaction mixture was stirred for another 1.5 hours at 0°C. Upon completion of the reaction, it was poured into saturated aqueous NH4Cl solution (100 mL) and extracted with EtOAc (100 mL × 2). The organic layers were combined, washed with brine (100 mL), dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 4% EtOAc in petroleum ether) to afford the title compound (850 mg, 58%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.82 (s, 1H), 6.50 (d, J = 16.4 Hz, 1H), 6.36 (dd, J = 16.4, 6.8 Hz, 1H), 3.99 (s, 3H), 2.24 - 2.22(m, 1H), 2.21 - 2.20 (m, 1H),2.19 - 2.00 (m, 4H), 1.43 - 1.39 (m, 2 H), 1.27 - 1.23 (m, 2H); LCMS (ESI): m/z 389.1 (M+H) ⁺ . [0591] Step 6: 3-((Diphenylmethylene)amino)-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)picolinonitrile [0592] To a mixture of 3-bromo-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)picolinonitrile (640 mg, 1.64 mmol) in 1,2-dimethoxyethane (30 mL) were added diphenylmethanimine (0.83 mL, 4.93 mmol), K ₃ PO ₄ (1.4 g, 6.58 mmol), t- BuXphos (69 mg, 0.16 mmol) and Pd2(dba)3 (150 mg, 0.16 mmol). The solution was stirred at 80°C for 3 hours under nitrogen atmosphere. Water (80 mL) was added into the reaction and the result mixture was extracted with EtOAc (80 mL × 2). The combined organic layers were washed with brine (80 mL), dried with Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 2% EtOAc in petroleum ether) to afford the title compound (800 mg, 99%) as a yellow solid. LCMS (ESI): m/z 490.7 (M+H) ⁺ . [0593] Step 7: 3-Amino-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)picolinonitrile [0594] To a solution of 3-((diphenylmethylene)amino)-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)picolinonitrile (800 mg, 1.63 mmol) in THF (8 ml) was added a 2N aqueous HCl solution (1.0 mL, 2.00 mmol). The mixture was stirred at room temperature for 30 minutes. The mixture was adjusted to pH 8 with saturated aqueous NaHCO3, and extracted with EtOAc (60 mL × 3). The combined organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 8 % EtOAc in petroleum ether) to afford the title compound (310 mg, 58%) as a yellow solid. LCMS (ESI): m/z 326.0 (M+H) ⁺ . [0595] Step 8: N-(2-Cyano-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0596] To the mixture of DIPEA (0.030 ml, 0.20 mmol) and 3-amino-6-methoxy-5-((E)- 2-(trans-4-(trifluoromethyl)cyclohexyl)vinyl)picolinonitrile (50 mg, 0.15 mmol) in DCM (2 mL) was added acryloyl chloride (0.010 ml, 0.18 mmol). The result reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with water (40 mL), and extracted with DCM (40 mL × 2). The combined organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by prep-TLC (20% EtOAc in petroleum ether) to afford the title compound (23 mg, 36%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 10.41 (s, 1H), 8.08 (s, 1H), 6.61 - 6.43 (m, 3H), 6.31 (d, J = 16.8 Hz, 1H), 5.86 (dd, J = 10.0, 1.6 Hz, 1H), 3.93 (s, 3H), 2.24 - 2.14 (m, 2H), 1.92 - 1.81 (m, 4H), 1.35 - 1.19 (m, 4H). LCMS (ESI): m/z 380.2 (M+H) ⁺ . EXAMPLE 14 [0597] Preparation of (E)-N-(3-(3-cyclopentylprop-1-en-1-yl)-4- methoxyphenyl)acrylamide [0598] The overall reaction scheme was as follows: [0599] Step 1: (E)-2-(3-Cyclopentylprop-1-en-1-yl)-4,4,5,5-tetramethyl-1,3, 2- dioxaborolane [0600] A mixture of HZrCp2Cl (602 mg, 2.34 mmol), prop-2-yn-1-ylcyclopentane (1.23 mL, 8.6 mmol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.13 mL, 7.81 mmol) was stirred at 60°C under a nitrogen atmosphere for 16 hours. The residue filtered through silica gel (0 - 20% ethyl acetate in petroleum ether) to afford the title compound (100 mg, 10% purity) as a colorless oil which was used directly in the next step without any further purification. [0601] Step 2: (E)-3-(3-Cyclopentylprop-1-en-1-yl)-4-methoxyaniline [0602] A mixture of Pd(dppf)Cl ₂ (54 mg, 0.070 mmol), (E)-2-(3-cyclopentylprop-1-en- 1-yl)- 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (351 mg, 1.48 mmol), Cs2CO3 (726 mg, 2.23 mmol) and 3-bromo-4-methoxyaniline (150 mg, 0.74 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was stirred at 80°C for 16 hours under a nitrogen atmosphere. The resulting solution was diluted with water (100 mL) and extracted with EtOAc (50 mL × 2). The organic layers were combined, dried over Na2SO4 and concentrated under vacuum. The residue was purified by pre-TLC (30% EtOAc in petroleum ether) to afford the title compound (30 mg, 18%) as a white solid. LCMS (ESI): m/z 232.3 (M+H) ⁺ . [0603] Step 3: (E)-N-(3-(3-cyclopentylprop-1-en-1-yl)-4-methoxyphenyl)acryl amide [0604] To a mixture of (E)-3-(3-cyclopentylprop-1-en-1-yl)-4-methoxyaniline (20 mg, 0.09 mmol) in DCM (2 mL) at 0°C was added DIPEA (0.030 mL, 0.17 mmol) and then acryloyl chloride (10 uL, 0.13 mmol) was added into the mixture. The reaction mixture was stirred for 2 hours then it was quenched by water (20 mL). The resulting solution was extracted with DCM (30 mL × 2) and the organic layers were combined. The organic layer was dried over Na ₂ SO ₄ and concentrated under vacuum. The residue was purified by pre-TLC (30% EtOAc in petroleum ether) to afford the title compound (6 mg, 23%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.59 (d, J = 2.4 Hz, 1H), 7.45 (dd, J = 8.8, 2.4 Hz, 1H), 7.17 (s, 1H), 6.82 (d, J = 8.8 Hz, 1H), 6.67 (d, J = 16.4 Hz, 1H), 6.43 (d, J = 16.4 Hz, 1H), 6.28 - 6.19 (m, 2H), 5.76 (d, J = 10.0 Hz, 1H), 3.84 (s, 3H), 2.26 - 2.21 (m, 2H), 2.00 - 1.89 (m, 1H), 1.82 - 1.74 (m, 2H), 1.65 - 1.61 (m, 2H), 1.56 - 1.49 (m, 2H), 1.24 - 1.15 (m, 2H); LCMS (ESI): m/z 286.2 (M+H) ⁺ . EXAMPLE 15 [0605] Preparation of N-(2-Hydroxyethyl)-N-(5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0606] The overall reaction scheme was as follows: [0607] Step 1: 2-((5-Methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)amino)ethanol [0608] To a mixture of 2-chloro-5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridine (2.0 g, 6.25 mmol) in DMSO (25 mL) were added 2- aminoethanol (0.56 mL, 9.38 mmol), N ¹ ,N ² -bis(2,4,6-trimethoxyphenyl)oxalamide (132 mg, 0.31 mmol), CuI (60 mg, 0.31 mmol) and K ₃ PO ₄ (1.33 g, 6.25 mmol). The mixture was stirred at 130°C for 16 hours under a nitrogen atmosphere. The mixture was diluted with water (100 mL) and the resultant mixture was extracted with EtOAc (50 mL× 2). The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by flash chromatography on silica gel (0 - 70% EtOAc in petroleum ether) to afford the title compound (1.0 g, 46%) as a brown oil. ¹ H NMR (400 MHz, CDCl3): δ 7.68 (s, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.50 (s, 1H), 6.28 (dd, J = 16.0, 7.2 Hz, 1H), 4.56 (s, 1H), 3.81 (s, 3H), 3.80 - 3.77 (m, 2H), 3.50 - 3.44 (m, 2H), 2.22 - 2.11 (m, 1H), 2.05 - 1.95 (m, 5H), 1.46 - 1.33 (m, 2H), 1.28 - 1.16 (m, 2H). [0609] Step 2: N-(2-Hydroxyethyl)-N-(5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)acrylamide [0610] To a mixture of 2-((5-methoxy-4-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)amino)ethanol (240 mg, 0.70 mmol) in DCM (6 mL) was added DIPEA (0.23 mL, 1.39 mmol). The mixture was stirred at 0°C for 5 minutes, then acryloyl chloride (70 uL, 0.84 mmol) was added into the mixture. The reaction was stirred at 0°C for 1 hour and was quenched by water (40 mL). The resulting solution was extracted with DCM (40 mL × 2) and the organic layers were combined. The organics were dried over Na2SO4 and concentrated under vacuum. The residue was purified by pre-TLC (30% EtOAc in petroleum ether) to afford the crude product which was further purified by reverse phase chromatography (Phenomenex Gemini NX-C18 (75*30mm*3um); water (0.2% FA)-ACN; 35/75) to afford the title compound (18 mg, 6%) as a colorless oil. ¹ H NMR (400 MHz, CDCl3): δ 8.07 (s, 1H), 7.17 (s, 1H), 6.63 (d, J = 16.4 Hz, 1H), 6.50 - 6.30 (m, 2H), 6.15 - 6.11 (m, 1H), 5.65 (d, J = 10.8 Hz, 1H), 4.95 - 4.93 (m, 1H), 4.03 - 3.99 (m, 2H), 3.98 (s, 3H), 3.88 - 3.83 (m, 2H), 2.27 - 2.14 (m, 1H), 2.07 - 1.96 (m, 5H), 1.47 - 1.34 (m, 2H), 1.30 - 1.17 (m, 2H); LCMS (ESI): m/z 399.2 (M+H) ⁺ . EXAMPLE 16 [0611] Preparation of N-(4-fluoro-4'-isopropyl-6-methoxy-[1,1'-biphenyl]-3- yl)acrylamide [0612] The overall reaction scheme was as follows: [0613] Step 1: 1-Bromo-4-fluoro-2-methoxy-5-nitrobenzene and 1-bromo-2-fluoro-4- methoxy-5-nitro-benzene [0614] To a stirred solution of 1-bromo-2,4-difluoro-5-nitro-benzene (12.1 g, 50.8 mmol) in MeOH (100 mL) was added 25% sodium methoxide in MeOH (12 mL, 53.4 mmol, 12 mL) at 0°C, and the reaction mixture was stirred at 0°C for 2 hours and then at RT for 20 hours. Volatile solvent was removed under reduced pressure, and the resultant residue was partitioned between ⁱ PrOAc and water. The organic layer was washed with water and brine, dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The crude product was purified by column chromatography (SiO ₂ : ⁱ PrOAc / heptane) to afford 10.9 g (86% yield) of a mixture of 1-bromo- 4-fluoro-2-methoxy-5-nitro-benzene and 1-bromo-2-fluoro-4-methoxy-5-nitro-benzene (~2:1 ratio).1-Bromo-4-fluoro-2-methoxy-5-nitrobenzene: ¹ H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.0 Hz, 1H), 6.77 (d, J = 12.3 Hz, 1H), 4.00 (s, 3H).1-Bromo-2-fluoro-4-methoxy-5-nitro- benzene: ¹ H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 7.1 Hz, 1H), 6.89 (d, J = 9.8 Hz, 1H), 3.97 (s, 3H). [0615] Step 2: 5-Bromo-2-fluoro-4-methoxyaniline and 5-bromo-4-fluoro-2- methoxyaniline [0616] To a mixture of 1-bromo-4-fluoro-2-methoxy-5-nitro-benzene and 1-bromo-2- fluoro-4-methoxy-5-nitro-benzene (~2:1 ratio) (6.1 g, 24.3 mmol) dissolved in EtOH (162 mL) was added ammonium chloride (13.0 g, 243.2 mmol) in water (49 mL), followed by iron powder (6.8 g, 121.6 mmol). The reaction mixture was stirred at reflux for 20 hours. The reaction mixture was cooled to RT and filtered through a pad of Celite®. The pad of rinsed well with DCM and EtOH. The filtrate was basified with sat. aq. NaHCO ₃ solution until pH ~7 and then extracted with ⁱ PrOAc (3x). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude products were purified by column chromatography (SiO ₂ : ⁱ PrOAc / heptane) to retrieve 3.3g (61% yield) of 5-bromo-2-fluoro-4- methoxyaniline followed by 2.0 g (36% yield) of 5-bromo-4-fluoro-2-methoxyaniline.5-Bromo- 2-fluoro-4-methoxyaniline: ¹ H NMR (400 MHz, CDCl3) δ 7.00 (d, J = 9.3 Hz, 1H), 6.66 (d, J = 12.1 Hz, 1H), 3.80 (s, 3H), 3.47 (s, 2H); MS (ESI+) m/z 220 (M+H) ⁺ .5-bromo-4-fluoro-2- methoxyaniline: ¹ H NMR (400 MHz, CDCl3) δ 6.82 (d, J = 6.9 Hz, 1H), 6.61 (d, J = 10.0 Hz, 1H), 3.83 (s, 3H), 3.68 (s, 2H); MS (ESI+) m/z 220 (M+H) ⁺ . [0617] Step 3: 2-Fluoro-5-(4-isopropylphenyl)-4-methoxy-aniline [0618] A screwed top flask was charged with 5-bromo-2-fluoro-4-methoxy-aniline (700 mg, 3.2 mmol), (4-isopropylphenyl)boronic acid (678 mg, 4.1 mmol), potassium phosphate (1.4 g, 6.4 mmol), SPhos pre-catalyst G3 (248 mg, 0.32 mmol), SPhos (234 mg, 0.54 mmol), toluene (10 mL), and water (1 mL). The reaction mixture was vacuum purged / back-filled with nitrogen (3X). The flask was screwed tightly with a cap, and the reaction mixture was stirred at 95°C for 18 hours. The cooled reaction mixture was diluted with ⁱ PrOAc and filtered through a pad of Celite®. The pad was rinsed with additional ⁱ PrOAc. The filtrate was washed with water and brine, dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The crude product was purified by column chromatography (SiO2: ⁱ PrOAc / heptane) to retrieve 2-fluoro-5-(4-isopropylphenyl)-4- methoxy-aniline (825 mg, 86.5% yield). ¹ H NMR (400 MHz, CDCl3) δ 7.46 – 7.41 (m, 2H), 7.32 – 7.27 (m, 2H), 6.80 (d, J = 10.1 Hz, 1H), 6.74 (d, J = 12.5 Hz, 1H), 3.73 (s, 3H), 3.48 (s, 2H), 3.03 – 2.91 (m, 1H), 1.32 (d, J = 6.9 Hz, 6H); MS (ESI+) m/z 260 (M+H) ⁺ . [0619] Step 4: N-(4-fluoro-4'-isopropyl-6-methoxy-[1,1'-biphenyl]-3-yl)acry lamide [0620] To a mixture of 2-fluoro-5-(4-isopropylphenyl)-4-methoxy-aniline (90 mg, 0.347 mmol), acrylic acid (50.5 mg, 0.69 mmol, 0.05 mL), and HATU (296 mg, 0.76 mmol,) in anhydrous DMF (3.5 mL) was added DIPEA (224 mg, 1.7 mmol, 224 mg, 0.30 mL), and the reaction mixture was stirred at RT for 20 hours. The reaction mixture was diluted with ⁱ PrOAc, and the organic layer was washed with water, 50% brine (2X), brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography (SiO ₂ : ⁱ PrOAc / heptane) followed by reverse-phase preparative HPLC to afford 32 mg (29% yield) of the title compound as a white solid. ¹ H NMR (400 MHz, DMSO-d6) δ 9.84 (s, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.40 – 7.32 (m, 2H), 7.31 – 7.24 (m, 2H), 7.10 (d, J = 12.8 Hz, 1H), 6.56 (dd, J = 17.0, 10.2 Hz, 1H), 6.23 (dd, J = 17.1, 2.0 Hz, 1H), 5.74 (dd, J = 10.2, 2.0 Hz, 1H), 3.77 (s, 3H), 2.97 – 2.85 (m, 1H), 1.23 (d, J = 6.9 Hz, 6H); LCMS (ESI): m/z 314.2 (M+H) ⁺ . EXAMPLE 17 [0621] Preparation of (E)-N-(7-(4-chlorostyryl)-2,3-dihydrobenzofuran-5-yl)acrylam ide [0622] The overall reaction scheme was as follows: [0623] Step 1: (E)-5-bromo-7-(4-chlorostyryl)-2,3-dihydrobenzofuran [0624] To a mixture of 5-bromo-2,3-dihydrobenzofuran-7-carbaldehyde (2.50 g, 11.0 mmol) 1-chloro-4-(diethoxyphosphorylmethyl)benzene (5.78 g, 22 mmol) in anhydrous THF (55 mL) was added potassium tert-butoxide (3.7 g, 33.0 mmol, 3743.9 mg), and the reaction mixture was stirred at RT under a nitrogen atmosphere for 16 hours. Volatile solvent was removed, and the crude residue was diluted with ⁱ PrOAc. The organic layer was washed with water and brine, dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The crude product was purified by column chromatography (SiO2: ⁱ PrOAc / heptane) to give (E)-5-bromo-7-(4-chlorostyryl)-2,3- dihydrobenzofuran (3.70 g, 91.3%) as an oil. ¹ H NMR (400 MHz, CDCl3) δ 7.45 – 7.39 (m, 2H), 7.36 (d, J = 2.1 Hz, 1H), 7.33 – 7.28 (m, 2H), 7.24 (d, J = 16.5 Hz, 1H), 7.18 (q, J = 1.4 Hz, 1H), 7.00 (d, J = 16.5 Hz, 1H), 4.66 (t, J = 8.8 Hz, 2H), 3.22 (t, J = 8.7 Hz, 2H). LCMS (ESI): m/z 335 (M+H) ⁺ . [0625] Step 2: (E)-7-(4-chlorostyryl)-2,3-dihydrobenzofuran-5-amine [0626] In a 20-mL vial was placed 5-bromo-7-[(E)-2-(4-chlorophenyl)vinyl]-2,3- dihydrobenzofuran (257 mg, 0.77 mmol), diphenylmethanimine (194 mg, 1.1 mmol), sodium tert-butoxide (147 mg, 1.54 mmol), bis(2-diphenylphosphinophenyl)ether (41 mg, 0.076 mmol), and tris(dibenzylidenteactone)dipalladium(0) (35 mg, 0.04 mmol). Degassed toluene (11 mL) was added. The vial was vacuum purged / back-filled with nitrogen (3x) and capped. The reaction mixture was stirred at 120°C for 18 hours. The reaction mixture was diluted with ⁱ PrOAc and water, and then filtered through a pad of Celite®. The biphasic layers were separated. The organic phase was washed with water and brine, dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude was purified by column chromatography (SiO2: iPrOAc / heptane) to obtain intermediate (E)-N-(7-(4-chlorostyryl)-2,3-dihydrobenzofuran-5-yl)- 1,1-diphenylmethanimine as an oil. To (E)-N-(7-(4-chlorostyryl)-2,3-dihydrobenzofuran-5-yl)- 1,1-diphenylmethanimine dissolved in THF (7.6 mL) was added 1N HCl (3.8 mL, 3.8 mmol), and the reaction mixture was stirred at RT for 2 hours. Volatile solvent was removed under reduced pressure. The crude product was diluted with DCM, basified with saturated aqueous NaHCO ₃ solution until it reached pH 8, and extracted with DCM (3x). The combined organic layers were washed with water and brine, dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude was purified by column chromatography (SiO2: ⁱ PrOAc / heptane) to give ((E)-7-(4-chlorostyryl)-2,3-dihydrobenzofuran-5-amine (208 mg, 63% yield) as a solid. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.46 – 7.39 (m, 2H), 7.32 – 7.24 (m, 2H), 7.21 (d, J = 16.4 Hz, 1H), 7.03 (d, J = 16.4 Hz, 1H), 6.60 (d, J = 2.4 Hz, 1H), 6.53 (d, J = 2.3 Hz, 1H), 4.58 (t, J = 8.6 Hz, 2H), 3.80 –3.00 (s, 2H), 3.15 (t, J = 8.6 Hz, 2H); LCMS (ESI): m/z 272 (M+H) ⁺ . [0627] Step 3: (E)-N-(7-(4-chlorostyryl)-2,3-dihydrobenzofuran-5-yl)acrylam ide [0628] The title compound (41 mg, 38.5%) was furnished as a white solid. It was prepared from (E)-7-(4-chlorostyryl)-2,3-dihydrobenzofuran-5-amine (34 mg, 0.13 mmol) and acrylic acid (45 mg, 0.63 mmol, 0.04 mL) following the procedure outlined for Example 16, step 4. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.00 (s, 1H), 7.64 – 7.56 (m, 3H), 7.47 (br s, 1H), 7.44 – 7.38 (m, 2H), 7.26 (d, J = 16.4 Hz, 1H), 7.15 (d, J = 16.4 Hz, 1H), 6.42 (dd, J = 17.0, 10.1 Hz, 1H), 6.23 (dd, J = 17.0, 2.1 Hz, 1H), 5.72 (dd, J = 10.1, 2.1 Hz, 1H), 4.63 (t, J = 8.7 Hz, 2H), 3.21 (t, J = 8.7 Hz, 2H); LCMS (ESI): m/z 326.1 (M+H) ⁺ . EXAMPLE 18 [0629] Preparation of (E)-N-(6-methoxy-5-(4-methylpent-1-en-1-yl)pyridin-3- yl)acrylamide [0630] The overall reaction scheme was as follows:

[0631] Step 1: (E)-5-bromo-2-methoxy-3-(4-methylpent-1-en-1-yl)pyridine [0632] (E)-5-bromo-2-methoxy-3-(4-methylpent-1-en-1-yl)pyridine (633 mg, 91%) was prepared from diethyl ((5-bromo-2-methoxypyridin-3-yl)methyl)phosphonate (873 mg, 2.6 mmol) and 3-methylbutanal (667 mg, 7.8 mmol) following the procedure outlined for Example 17, step 1. ¹ H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 2.5 Hz, 1H), 7.71 (dd, J = 2.5, 0.5 Hz, 1H), 6.45 (dt, J = 15.9, 1.4 Hz, 1H), 6.27 (dt, J = 15.9, 7.3 Hz, 1H), 3.94 (s, 3H), 2.14 - 2.09 (m, 2H), 1.79 - 1.67 (m, 1H), 0.94 (d, J = 6.7 Hz, 6H); LCMS (ESI): m/z 332 (M+H) ⁺ . [0633] Step 2: (E)-6-methoxy-5-(4-methylpent-1-en-1-yl)pyridin-3-amine [0634] (E)-6-methoxy-5-(4-methylpent-1-en-1-yl)pyridin-3-amine (148 mg, 51%) was prepared from (E)-5-bromo-2-methoxy-3-(4-methylpent-1-en-1-yl)pyridine (380 mg, 1.4 mmol) following the procedure outlined for Example 17, step 2. LCMS (ESI): m/z 207 (M+H) ⁺ . [0635] Step 3: (E)-N-(6-methoxy-5-(4-methylpent-1-en-1-yl)pyridin-3-yl)acry lamide [0636] The title compound (9.1 mg, 8.7%) was furnished as a white solid. It was prepared from (E)-6-methoxy-5-(4-methylpent-1-en-1-yl)pyridin-3-amine (83 mg, 0.40 mmol) and acrylic acid (146 mg, 2.0 mmol) following the procedure outlined for Example 17, step 3. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.15 (s, 1H), 8.29 (d, J = 2.5 Hz, 1H), 8.08 (d, J = 2.5 Hz, 1H), 6.47 (d, J = 16.0, 1H), 6.40 (dd, J = 17.0, 10.1 Hz, 1H), 6.35 - 6.20 (m, 2H), 5.76 (dd, J = 10.1, 2.1 Hz, 1H), 3.87 (s, 3H), 2.14 - 2.08 (m, 2H), 1.80 - 1.65 (m, 1H), 0.91 (d, J = 6.6 Hz, 6H); LCMS (ESI): m/z 261.2 (M+H) ⁺ . EXAMPLE 19 [0637] Preparation of (E)-N-(5-(2-(3,3-difluorocyclobutyl)vinyl)-6-methoxypyridin- 3- yl)acrylamide [0638] The overall reaction scheme was as follows: [0639] Step 1: (E)-5-bromo-3-(2-(3,3-difluorocyclobutyl)vinyl)-2-methoxypyr idine [0640] (E)-5-bromo-3-(2-(3,3-difluorocyclobutyl)vinyl)-2-methoxypyr idine (630 mg, 96.5%) was prepared from diethyl ((5-bromo-2-methoxypyridin-3-yl)methyl)phosphonate (700 mg, 2.1 mmol) and 3,3-difluorocyclobutanecarbaldehyde (2486 mg, 20.7 mmol) following the procedure outlined for Example 17, step 1. ¹ H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 2.4 Hz, 1H), 7.70 (d, J = 2.3 Hz, 1H), 6.48 (dd, J = 16.0, 1.0 Hz, 1H), 6.33 (dd, J = 15.9, 7.3 Hz, 1H), 3.94 (s, 3H), 3.02 – 2.90 (m, 1H), 2.90 – 2.75 (m, 2H), 2.56 – 2.40 (m, 2H); LCMS (ESI): m/z 304 (M+H) ⁺ . [0641] Step 2: (E)-5-(2-(3,3-difluorocyclobutyl)vinyl)-6-methoxypyridin-3-a mine [0642] (E)-5-(2-(3,3-difluorocyclobutyl)vinyl)-6-methoxypyridin-3-a mine (210 mg, 58%) was prepared from (E)-5-bromo-3-(2-(3,3-difluorocyclobutyl)vinyl)-2-methoxypyr idine (456 mg, 1.5 mmol) following the procedure outlined for Example 17, step 2. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.56 (d, J = 2.8 Hz, 1H), 7.09 (dd, J = 2.9, 0.6 Hz, 1H), 6.53 (dd, J = 15.9, 1.1 Hz, 1H), 6.29 (dd, J = 15.9, 7.5 Hz, 1H), 3.91 (s, 3H), 3.35 (s, 2H), 3.02 - 2.90 (m, 1H), 2.90 - 2.76 (m, 2H), 2.57 - 2.40 (m, 2H); LCMS (ESI): m/z 241 (M+H) ⁺ . [0643] Step 3: (E)-N-(5-(2-(3,3-difluorocyclobutyl)vinyl)-6-methoxypyridin- 3- yl)acrylamide [0644] The title compound (21 mg, 28.7%) was furnished as a white solid. It was prepared from (E)-5-(2-(3,3-difluorocyclobutyl)vinyl)-6-methoxypyridin-3-a mine (60 mg, 0.25 mmol) and acrylic acid (91 mg, 1.3 mmol) following the procedure outlined for Example 17, step 3. ¹ H NMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 8.27 (d, J = 2.5 Hz, 1H), 8.13 (d, J = 2.6 Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 6.48 - 6.35 (m, 2H), 6.26 (dd, J = 17.0, 2.0 Hz, 1H), 5.77 (dd, J = 10.1, 2.1 Hz, 1H), 3.88 (s, 3H), 3.07 - 2.94 (m, 1H), 2.90 - 2.76 (m, 2H), 2.60 - 2.45 (m, 2H); LCMS (ESI): m/z 295.2 (M+H) ⁺ . EXAMPLE 20 [0645] Preparation of (E)-N-(5-(2-(4,4-Difluorocyclohexyl)vinyl)-6-methoxypyridin- 3- yl)-2-phenylacrylamide [0646] The overall reaction scheme was as follows:

[0647] Step 1: 2-Phenylacryloyl chloride [0648] To a mixture of 2-phenylacrylic acid (500 mg, 3.37 mmol) and one drop DMF in dichloromethane (5 mL) was added (COCl)2 (0.57 mL, 6.75 mmol) at 0°C dropwise. The mixture was stirred at 0°C for 2 hours. The reaction mixture was concentrated to afford the title compound (400 mg, 71%) as a colorless liquid. The crude was used for the next step without further purification. [0649] Step 2: (E)-N-(5-(2-(4,4-Difluorocyclohexyl)vinyl)-6-methoxypyridin- 3-yl)-2- phenylacrylamide [0650] To the mixture of (E)-5-(2-(4,4-difluorocyclohexyl)vinyl)-6-methoxypyridin-3- amine (Intermediate G, 150 mg, 0.56 mmol), DIPEA (0.28 mL, 1.68 mmol) and 4- dimethylaminopyridine (3.42 mg, 0.03 mmol) in dichloromethane (2 mL) was added 2- phenylacryloyl chloride (400 mg, 2.40 mmol) at 0°C dropwise. The resulting mixture was stirred at 0°C for 2 hours. The solution was quenched with H2O (20 mL). The resulting solution was extracted with EtOAc (20 mL × 2), washed with H ₂ O (10 mL × 2). And the combined organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by pre-HPLC (Boston Green ODS 150*30mm*5um, water (0.2% FA)-ACN, 65 - 95%) to afford the title compound (30.52 mg, 14%) as white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.22 (s, 1H), 8.33 (d, J = 2.0 Hz, 1H), 8.13 (d, J = 2.0 Hz, 1H), 7.53 - 7.45 (m, 2H), 7.43 - 7.33 (m, 3H), 6.53 (d, J = 16.0 Hz, 1H), 6.28 (dd, J = 16.0, 7.2 Hz, 1H), 5.94 (s, 1H), 5.79 (s, 1H), 3.88 (s, 3H), 2.41 - 2.30 (m, 1H), 2.11 - 1.98 (m, 2H), 1.97 - 1.77 (m, 4H), 1.52 - 1.34 (m, 2H). LCMS (ESI): m/z 399.2 (M+H) ⁺ . EXAMPLE 21 [0651] Preparation of (E)-3-cyano-N-(5-((E)-2-(4,4-difluorocyclohexyl)vinyl)-6- methoxypyridin-3-yl)acrylamide [0652] The title compound (75.05 mg, 39%) was furnished as a white solid. It was prepared from (E)-5-(2-(4,4-difluorocyclohexyl)vinyl)-6-methoxypyridin-3-a mine (Intermediate G, 150 mg, 0.56 mmol) and (E)-3-cyanoacrylic acid (100 mg, 1.03 mmol) following the procedure outlined for Example 1, Step 4. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.11 (d, J = 2.4 Hz, 1H), 8.08 (d, J = 2.4 Hz, 1H), 7.45 (s, 1H), 6.88 (d, J = 16.0 Hz, 1H), 6.72 - 6.51 (m, 2H), 6.26 (dd, J = 16.0, 7.2 Hz, 1H), 3.98 (s, 3H), 2.35 - 2.22 (m, 1H), 2.19 - 2.10 (m, 2H), 1.90 - 1.84 (m, 2H), 1.85 - 1.71 (m, 2H), 1.59 - 1.51 (m, 2H). LCMS (ESI): m/z 348.1 (M+H) ⁺ . EXAMPLE 22 [0653] Preparation of N-(4-Methoxy-3-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)phenyl)acrylamide [0654] The overall reaction scheme was as follows: [0655] Step 1: Diethyl 5-bromo-2-methoxybenzylphosphonate [0656] A mixture of 4-bromo-2-(bromomethyl)-1-methoxybenzene (4.0 g, 14.29 mmol) and triethyl phosphite (9.00 mL, 155.17 mmol) were stirred at 130°C for 3 hours. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (0 - 50% EtOAc in petroleum ether) to afford the title compound (5.3 g, 88%) as a light yellow oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 7.41 - 7.38 (m, 2H), 6.97 - 6.95 (m, 1H), 3.98 - 3.89 (m, 4H), 3.78 (s, 3H), 3.18 (d, J = 22.0, 2H), 1.16 (t, J = 7.2 Hz, 6H). [0657] Step 2: 4-Bromo-1-methoxy-2-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)benzene [0658] To a solution of diethyl 5-bromo-2-methoxybenzylphosphonate (500 mg, 1.48 mmol) in toluene (10 mL) at 0°C was added sodium tert-pentoxide (71 mg, 2.97 mmol) After being stirred at 0°C for 20 minutes, a solution of trans-4-(trifluoromethyl) cyclohexanecarbaldehyde (Intermediate A, 267 mg, 1.48 mmol) in THF (10 mL) was added dropwise and the reaction mixture was stirred for 1.5 hours at 0°C. The reaction mixture was poured into saturated aqueous NH4Cl solution (20 mL) and extracted with EtOAc (30 mL × 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 5% EtOAc in petroleum ether) to afford the title compound (540 mg, 90%) as a colorless oil. ¹ H NMR (400 MHz, DMSO-d6): δ 7.57 (d, J = 2.4 Hz, 1H), 7.35 (dd, J = 8.8, 2.4 Hz, 1H), 6.94 (d, J = 8.8 Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.26 (dd, J=16.0, 6.8 Hz, 1H), 3.78 (s, 3H), 2.31 - 2.17 (m, 1H), 2.17 - 2.06 (m, 1H), 1.91 - 1.82 (m, 4H), 1.34 - 1.20 (m, 4H). [0659] Step 3: 1-(4-Chlorobenzyl)-3-methyl-6-nitro-1H-indole [0660] To a solution of 4-bromo-1-methoxy-2-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)benzene (540 mg, 1.49 mmol) in DMSO (2 mL) were added CuI (29 mg, 0.15 mmol), K ₃ PO ₄ (1188 mg, 4.46 mmol), NH ₃ ^. H ₂ O (0.27 mL, 3.57 mmol) and N ¹ ,N ² -bis(5-methyl-[1,1'-biphenyl]-2-yl)oxalamide (62 mg, 0.15 mmol). The reaction mixture was stirred at 120°C for 16 hours under N2. The reaction was diluted with water (10 mL), extracted with EtOAc (20 mL × 3) and the combined organic layers were dried with Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 2% EtOAc in petroleum ether) to afford the title compound (300 mg, 67%) as a brown solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 6.72 - 6.63 (m, 2H), 6.51 (d, J = 16.0 Hz, 1H), 6.46 - 6.39 (m, 1H), 5.99 (dd, J = 16.0, 6.8 Hz, 1H), 4.58 (s, 2H), 3.64 (s, 3H), 2.31 - 2.17 (m, 1H), 2.15 - 2.03 (m, 1H), 1.92 - 1.82 (m, 4H), 1.34 - 1.23 (m, 4H). [0661] Step 4: N-(4-Methoxy-3-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)phenyl)acrylamide [0662] The title compound (90.6 mg, 77%) was furnished as a white solid. It was prepared from 4-methoxy-3-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl)viny l)aniline (200 mg, 0.75 mmol) and acryloyl chloride (0.06 mL, 0.75 mmol) following the procedure outlined for Example 2. It was purified via prep-TLC (3% EtOAc in petroleum ether). ¹ H NMR (400 MHz, DMSO-d6): δ 10.01 (s, 1H), 7.74 (d, J = 2.4 Hz, 1H), 7.49 (dd, J = 8.8, 2.4 Hz, 1H), 6.94 (d, J = 8.8 Hz, 1H), 6.60 (d, J = 15.6 Hz, 1H), 6.35 (dd, J = 15.6, 10.0 Hz, 1H), 6.20 (d, J = 16.0 Hz, 1H), 6.07 (dd, J = 16.0, 7.2 Hz, 1H), 5.72 (dd, J = 10.0, 2.0 Hz, 1H), 3.76 (s, 3H), 2.21 - 2.07 (m, 2H), 1.91 - 1.84 (m, 4H), 1.35 - 1.22 (m, 4H). LCMS (ESI): m/z 354.1 (M+H) ⁺ . EXAMPLE 23 [0663] Preparation of (E)-N-(3-(2-(4,4-Difluorocyclohexyl)vinyl)-4- methoxyphenyl)acrylamide [0664] The overall reaction scheme was as follows: [0665] Step 1: (E)-4-Bromo-2-(2-(4,4-difluorocyclohexyl)vinyl)-1-methoxyben zene [0666] The title compound (140 mg, 14%) was furnished as a colorless oil. It was prepared from diethyl 5-bromo-2-methoxybenzylphosphonate (1.0 g, 2.97 mmol) and 4,4- difluorocyclohexanecarbaldehyde (Intermediate B, 880 mg, 2.97 mmol) following the procedure outlined for Example 22, Step 2. ¹ H NMR (400 MHz, DMSO-d6): δ 7.61 (d, J = 2.4 Hz, 1H), 7.35 (dd, J = 8.8, 2.4 Hz, 1H), 6.94 (d, J = 8.8 Hz, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.32 (dd, J = 16.0, 7.2 Hz, 1H), 3.78 (s, 3H), 2.32 - 2.28 (m, 1H), 2.05 - 1.99 (m, 2H), 1.92 - 1.78 (m, 4H), 1.44 - 1.38 (m, 2H). [0667] Step 2: (E)-3-(2-(4,4-difluorocyclohexyl)vinyl)-4-methoxyaniline [0668] The title compound (50 mg, 41%) was furnished as a brown solid. It was prepared from (E)-4-bromo-2-(2-(4,4-difluorocyclohexyl)vinyl)-1-methoxyben zene (140 mg, 0.45 mmol) following the procedure outlined for Example 22, Step 3. LCMS (ESI): m/z 268.2 (M+H) ⁺ . [0669] Step 3: (E)-N-(3-(2-(4,4-Difluorocyclohexyl)vinyl)-4-methoxyphenyl)a crylamide [0670] The title compound (32.41 mg, 54%) was furnished as a white solid. It was prepared from (E)-3-(2-(4,4-difluorocyclohexyl)vinyl)-4-methoxyaniline (50 mg, 0.19 mmol) and acryloyl chloride (0.02 mL, 0.22 mmol) following the procedure outlined for Example 22, Step 4. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.00 (s, 1H), 7.72 (d, J = 2.4 Hz, 1H), 7.50 (dd, J = 8.8, 2.4 Hz, 1H), 6.94 (d, J = 8.8 Hz, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 10.0 Hz, 1H, 1H), 6.20 (d, J = 16.0 Hz, 1H), 6.10 (dd, J = 16.0, 7.2 Hz, 1H), 5.71 (dd, J = 10.0, 2.0 Hz, 1H), 3.76 (s, 3H), 2.33 - 2.30 (m, 1H), 2.04 - 1.95 (m, 2H), 1.91 - 1.80 (m, 4H), 1.46 - 1.37 (m, 2H). LCMS (ESI): m/z 322.1 (M+H) ⁺ . EXAMPLE 24 [0671] Preparation of N-(6-Methoxy-2-phenyl-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0672] The overall reaction scheme was as follows: [0673] Step 1: 5-Chloro-6-methoxy-3-nitropyridin-2-amine [0674] A mixture of 6-methoxy-3-nitropyridin-2-amine (1.0 g, 5.91 mmol) and NCS (870 mg, 6.5 mmol) in DMF (20 mL) was stirred at 80°C for 2 hours. The reaction solution was poured into water (50 mL) and extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine (50 mL × 2), dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 20% EtOAc in petroleum ether) to afford the title compound (1.0 g, 83%) as a brown solid. ¹ H NMR (400 MHz, CDCl3): δ 8.39 (s, 1H), 4.03 (s, 3H); LCMS (ESI): m/z 204.0 (M+H) ⁺ . [0675] Step 2: 2-Bromo-5-chloro-6-methoxy-3-nitropyridine [0676] To a solution of 5-chloro-6-methoxy-3-nitropyridin-2-amine (800 mg, 3.93 mmol) and CuBr ₂ (1.5 g, 6.68 mmol) in MeCN (80 mL) was added t-BuONO (810 mg, 7.86 mmol). The reaction solution was stirred for 2 hours at 60°C. The reaction solution was poured into water (50 mL) and extracted with EtOAc (50 mL × 2). The organic layers were washed with brine (50 mL), dried with Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 20% EtOAc in petroleum ether) to afford the title compound (560 mg, 53%) as a brown solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.30 (s, 1H), 4.15 (s, 3H). [0677] Step 3: 3-Chloro-2-methoxy-5-nitro-6-phenylpyridine [0678] A mixture of 2-bromo-5-chloro-6-methoxy-3-nitropyridine (500 mg, 1.87 mmol), phenylboronic acid (273 mg, 2.24 mmol), Pd(dppf)Cl ₂ (137 mg, 0.19 mmol), Na ₂ CO ₃ (594 mg, 5.61 mmol) in 1,4-dioxane (30 mL) and water (6 mL) was stirred at 100°C for 1 hour. The reaction was diluted with water (50 mL), extracted with EtOAc (50 mL × 3) and the combined organic layers were dried with Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 15% EtOAc in petroleum ether) to afford the title compound (407 mg, 82%) as a brown solid. ¹ H NMR (400 MHz, CDCl3): δ 8.25 (s, 1H), 7.55 - 7.53 (m, 2H), 7.50 - 7.46 (m, 3H), 4.15 (s, 3H); LCMS (ESI): m/z 264.9 (M+H) ⁺ . [0679] Step 4: 2-Methoxy-5-nitro-6-phenyl-3-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridine [0680] A solution of 3-chloro-2-methoxy-5-nitro-6-phenylpyridine (570 mg, 2.15 mmol), 4,4,5,5-tetramethyl-2-((E)-2-(trans-4-(trifluoromethyl)cyclo hexyl)vinyl)-1,3,2- dioxaborolane (790 mg, 2.58 mmol), K3PO4 (1.37 g, 6.46 mmol), Xphos (103 mg, 0.22 mmol) and Xphos Pd G ₃ (182 mg, 0.22 mmol) in 1,4-dioxane (20 mL) and water (4 mL) was stirred at 100°C for 2 hours. The reaction was diluted with water (50 mL), extracted with EtOAc (50 mL × 3) and the combined organic layers were dried with Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 15% EtOAc in petroleum ether) to afford the title compound (700 mg, 80%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.18 (s, 1H), 7.57 - 7.55 (m, 2H), 7.46 - 7.45 (m, 3H), 6.55 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 6.8 Hz, 1H), 4.09 (s, 3H), 2.24 - 2.22 (m, 1H), 2.21 - 1.98 (m, 5H), 1.43 - 1.39 (m, 2 H), 1.27 - 1.23 (m, 2H); LCMS (ESI): m/z 407.1 (M+H) ⁺ . [0681] Step 5: 6-Methoxy-2-phenyl-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-amine [0682] To a solution of 2-methoxy-5-nitro-6-phenyl-3-((E)-2-(trans-4-(trifluoromethy l) cyclohexyl)vinyl)pyridine (300 mg, 0.74 mmol) and NH4Cl (390 mg, 7.38 mmol) in THF (15 mL) and water (15 mL) was added iron powder (21 mg, 3.69 mmol). The mixture was stirred for 16 hours at 70°C. After filtration, the filtrate was extracted with EtOAc (50 mL × 2) and water (50 mL). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated to afford the title compound (250 mg, 90%) as a brown solid. LCMS (ESI): m/z 377.2 (M+H) ⁺ . [0683] Step 6: N-(6-Methoxy-2-phenyl-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0684] To a mixture of 6-methoxy-2-phenyl-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl) pyridin-3-amine (150 mg, 0.40 mmol) and TEA (0.11 mL, 0.80 mmol) in DCM (30 mL) was added acryloyl chloride (43 mg, 0.48 mmol) at 0°C. The mixture was stirred at 0°C for 1 hour. The reaction was quenched with water (20 mL), extracted with DCM (30 mL × 2). The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified pre-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 75/100) to afford the title compound (32.1 mg, 18%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.58 s, 1H), 7.65 - 7.63 (m, 2H), 7.52 - 7.44 (m, 3H), 6.59 (d, J = 16.0 Hz, 1H), 6.40 - 6.33 (m, 2H), 6.15 - 6.13 (dd, J = 16.8, 10.8 Hz, 1H), 5.75 (d, J = 10.8 Hz, 1H), 3.99 (s, 3H), 2.19 - 2.16 (m, 1H), 2.04 - 1.97 (m, 5H), 1.42 - 1.35 (m, 2H), 1.30 - 1.23 (m, 2H); LCMS (ESI): m/z 431.2 (M+H) ⁺ . EXAMPLE 25 [0685] Preparation of N-(2-(Hydroxymethyl)-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0686] The overall reaction scheme was as follows: [0687] Step 1: Methyl 5-chloro-6-methoxy-3-nitropicolinate [0688] A mixture of 2-bromo-5-chloro-6-methoxy-3-nitropyridine (3.0 g, 11.22 mmol), Pd(dppf)Cl2 (410 mg, 0.56 mmol) and TEA (5.67 g, 56.08 mmol) in methanol (150 mL) was stirred at 60°C for 16 hours under CO (15 Psi). The reaction solution was concentrated. The residue was purified by chromatography on silica gel (0 - 20% EtOAc in petroleum ether) to afford the title compound (1.7 g, 61%) as a brown oil. ¹ H NMR (400 MHz, CDCl3): δ 8.43 (s, 1H), 4.16 (s, 3H), 4.02 (s, 3H). [0689] Step 2: Methyl 3-amino-5-chloro-6-methoxypicolinate [0690] To a mixture of methyl methyl 5-chloro-6-methoxy-3-nitropicolinate (2.0 g, 8.11 mmol) and NH ₄ Cl (4.34 g, 81.1 mmol) in THF (100 mL) and water (100 mL) was added iron powder (2.26 g, 40.55 mmol), the mixture was stirred for 16 hours at 70°C. The reaction solution was filtrated and extracted with EtOAc (50 mL × 2), concentrated to afford the title compound (1.5 g, 85%) as a brown solid. LCMS (ESI): m/z 217.0 (M+H) ⁺ . [0691] Step 3: (3-Amino-5-chloro-6-methoxypyridin-2-yl)methanol [0692] A mixture of methyl methyl 3-amino-5-chloro-6-methoxypicolinate (400 mg, 1.85 mmol) and LiAlH4 (210 mg, 5.54 mmol) in THF (30 mL) was stirred at 0°C for 0.5 hour. The reaction solution was quenched with water (0.2 mL), 15% NaOH solution (0.2 mL), H2O (0.2 mL). The solution was dried over MgSO ₄ , filtrated and concentrated to afford the title compound (330 mg, 95%) as a yellow oil. ¹ H NMR (400MHz, CDCl ₃ ): δ 7.12 (s, 1H), 4.62 (s, 2H), 3.98 (s, 3H), 3.49 (s, 2H), 3.43 (s, 1H). [0693] Step 4: (3-Amino-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-2-yl)methanol [0694] The title compound (280 mg, 53%) was furnished as a brown oil. It was prepared from (3-amino-5-chloro-6-methoxypyridin-2-yl)methanol (300 mg, 1.59 mmol) and 4,4,5,5- tetramethyl-2-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl)vi nyl)-1,3,2-dioxaborolane (580 mg, 1.91 mmol) following the procedure outlined for Example 24, Step 4. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.10 (s, 1H), 6.52 (d, J = 16.0 Hz, 1H), 6.14 (dd, J = 16.0, 6.8 Hz, 1H), 4.61 (d, J = 2.8 Hz, 2H), 3.94 (s, 3H), 3.81 (s, 1H), 3.33 (s, 2H), 2.24 - 2.22 (m, 1H), 2.21 - 1.96 (m, 5H), 1.42 - 1.38 (m, 2 H), 1.27 - 1.24 (m, 2H); LCMS (ESI): m/z 331.1 (M+H) ⁺ . [0695] Step 5: N-(2-(Hydroxymethyl)-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0696] The title compound (7.46 mg, 6%) was furnished as a white solid. It was prepared from (3-amino-6-methoxy-5-((E)-2-(trans-4-(trifluoromethyl)cycloh exyl) vinyl)pyridin-2- yl)methanol (100 mg, 0.30 mmol) and acryloyl chloride (33 mg, 0.36 mmol) following the procedure outlined for Example 24, Step 6. It was purified by pre-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 60/90). ¹ H NMR (400 MHz, CDCl3): δ 8.28 (s, 1H), 7.99 (s, 1H), 6.53 (d, J = 16.4 Hz, 1H), 6.44 (d, J = 16.4 Hz, 1H), 6.31 - 6.22 (m, 2H), 5.81 (d, J = 10.0 Hz, 1H), 4.73 (s, 2H), 3.96 (s, 3H), 3.16 (s, 1H), 2.16 - 2.10 (m, 1H), 2.09 - 1.94 (m, 5H), 1.42 - 1.35 (m, 2H), 1.30 - 1.20 (m, 2H); LCMS (ESI): m/z 385.1 (M+H) ⁺ . EXAMPLE 26 [0697] Preparation of N-(2,6-Dimethoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0698] The overall reaction scheme was as follows: [0700] To a solution of 5-chloro-6-methoxy-3-nitropyridin-2-amine (1.0 g, 4.91 mmol) in 0.5 N HCl/MeOH (25 mL) was added t-BuONO (2.5 g, 24.56 mmol) at 0°C. The reaction solution was stirred at room temperature for 16 hours. The reaction solution was concentrated. Then water (100 mL) was added into the residue. The pH was adjusted to 9 with 1 M NaOH and extracted with EtOAc (100 mL × 2). The organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (400 mg, 37%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.45 s, 1H), 4.14 (s, 3H), 4.13 (s, 3H). [0701] Step 2: 5-Chloro-2,6-dimethoxypyridin-3-amine [0702] To a mixture of 3-chloro-2,6-dimethoxy-5-nitropyridine (400 mg, 1.83 mmol) and NH ₄ Cl (980 mg, 18.3 mmol) in THF (20 mL) and water (20 mL) was added iron powder (510 mg, 9.15 mmol). The mixture was stirred for 16 hours at 70°C. The reaction solution was filtrated and washed with EtOAc (30 mL × 3). The organic layer was extracted with H2O (50 mL). The organic layer was dried over Na2SO4 and concentrated to afford the title compound (300 mg, 87%) as a brown oil. LCMS (ESI): m/z 188.9 (M+H) ⁺ . [0703] Step 3: 2,6-Dimethoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-amine [0704] The title compound (300 mg, 57%) was furnished as a yellow solid l. It was prepared from 5-chloro-2,6-dimethoxy-pyridin-3-amine (300 mg, 1.59 mmol) and 4,4,5,5- tetramethyl-2-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl)vi nyl)-1,3,2-dioxaborolane (580 mg, 1.91 mmol) following the procedure outlined for Example 24, Step 4. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.07 (s, 1H), 6.49 (d, J = 16.0 Hz, 1H), 5.94 (dd, J = 16.0, 6.8 Hz, 1H), 3.97 (s, 3H), 3.90 (s, 3H), 3.37 (s, 2H), 2.24 - 2.22 (m, 1H), 2.21 - 1.94 (m, 5H), 1.43 - 1.36 (m, 2 H), 1.27 - 1.19 (m, 2H); LCMS (ESI): m/z 331.1 (M+H) ⁺ . [0705] Step 4: N-(2,6-Dimethoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)acrylamide [0706] The title compound (84.64 mg, 47%) was furnished as a white solid. It was prepared from 2,6-dimethoxy-5-((E)-2-(trans-4-(trifluoromethyl)cyclohexyl) vinyl) pyridin-3- amine (150 mg, 0.45 mmol) and acryloyl chloride (49 mg, 0.54 mmol) following the procedure outlined for Example 24, Step 6. It was purified pre-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 70/100) to afford the title compound. ¹ H NMR (400 MHz, CDCl3): δ 8.77 s, 1H), 7.48 s, 1H), 6.51 (d, J = 16.0 Hz, 1H), 6.43 (d, J = 16.8 Hz, 1H), 6.29 (dd, J = 16.8, 10.4 Hz, 1H), 6.10 (dd, J = 16.0 Hz, 6.8 Hz, 1H), 5.77 (d, J = 10.4 Hz, 1H), 4.01 (s, 3H), 3.94 (s, 3H), 2.16 - 2.10 (m, 1H), 2.09 - 1.93 (m, 5H), 1.42 - 1.35 (m, 2H), 1.30 - 1.19 (m, 2H); LCMS (ESI): m/z 385.1 (M+H) ⁺ . EXAMPLE 27 [0707] Preparation of (E)-N-(4-(2-(4,4-Difluorocyclohexyl)vinyl)-5-methoxypyrimidi n- 2-yl)acrylamide [0708] The overall reaction scheme was as follows:

[0710] To a solution of compound 2,4-dichloro-5-methoxypyrimidine (5.0 g, 27.9 mmol) and Fe(acac) ₃ (1.0 g, 2.8 mmol) in THF (50 mL) was added dropwise methylmagnesiumbromide (18.6 mL, 55.9 mmol, 3.0 mol/L in 2-methyltetrahydrofuran) at 0°C. The reaction mixture was stirred at 0°C for 4 hours. The mixture was diluted with water (300 mL) and the mixture was extracted with EtOAc (300 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (2.9 g, 66%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.07 (s, 1H), 3.93 (s, 3H), 2.46 (s, 3H). [0711] Step 2: 4-(Bromomethyl)-2-chloro-5-methoxypyrimidine [0712] A mixture of AIBN (100 mg, 0.63 mmol), NBS (3.1 g, 17.6 mmol) and 2-chloro- 5-methoxy-4-methyl-pyrimidine (2.0 g, 12.6 mmol) in CCl ₄ (60 mL) was stirred at 80°C under N ₂ for 16 hours. Water (30 mL) was added to the solution and the mixture was extracted with EtOAc (30 mL × 2). The combined organic layers were washed with brine (30 mL), dried with Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 20% EtOAc in petroleum ether) to afford to afford the title compound (2.7 g, 50% purity, residual starting materials) as a yellow oil. ¹ H NMR (400 MHz, CDCl3): δ 8.26 (s, 1H), 4.46 (s, 2H), 4.02 (s, 3H). [0713] Step 3: Diethyl ((2-chloro-5-methoxypyrimidin-4-yl)methyl)phosphonate [0714] A mixture of 4-(bromomethyl)-2-chloro-5-methoxy-pyrimidine (2.6 g, 5.5 mmol) and triethyl phosphite (1.0 mL, 17.2 mmol) were stirred at 130°C for 3 hours. The reaction was concentrated and the residue was purified by column chromatography on silica gel (0 - 30% EtOAc in petroleum ether) to afford the title compound (1.5 g, 93%) as a colorless oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.17 (s, 1H), 4.17 - 4.12 (m, 4H), 3.46 (d, J = 26.8 Hz, 2H), 2.77 (s, 3H), 1.34 - 1.31 (m, 6H). [0715] Step 4: (E)-2-Chloro-4-(2-(4,4-difluorocyclohexyl)vinyl)-5-methoxypy rimidine [0716] To a solution of diethyl ((2-chloro-5-methoxypyrimidin-4-yl)methyl)phosphonate (1.2 g, 4.07 mmol) in toluene (20 mL) at 0°C was added sodium tert-pentoxide (600 mg, 5.45 mmol). After being stirred at 0°C for 20 minutes, a solution of 4,4- difluorocyclohexanecarbaldehyde (Intermediate B, 1.2 g, 8.14 mmol) in THF (20 mL) was added dropwise and the reaction mixture was stirred for 1.5 h at 0°C. The reaction mixture was poured into saturated aqueous solution of NH4Cl (50 mL) and extracted with EtOAc (100 mL × 2). The organic layers were combined, washed with brine (50 mL), dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 20% EtOAc in petroleum ether) to afford the title compound (700 mg, 60%) as a colorless oil. ¹ H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 2.0 Hz, 1H), 7.22 (dd, J =15.6, 6.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 3.95 (s, 3H), 2.36 - 3.34 (m, 1H), 2.17 - 2.15 (m, 2H), 1.94 - 1.90 (m, 2H), 1.86 - 1.73 (m, 2H), 1.70 - 1.62 (m, 2H). [0717] Step 5: (E)-tert-Butyl (4-(2-(4,4-difluorocyclohexyl)vinyl)-5-methoxypyrimidin- 2-yl)carbamate [0718] A mixture of (E)-2-chloro-4-(2-(4,4-difluorocyclohexyl)vinyl)-5- methoxypyrimidine (200 mg, 0.69 mmol), tert-butyl carbamate (243 mg, 2.08 mmol), K2CO3 (287 mg, 2.08 mmol), Pd(OAc)2 (16 mg, 0.07 mmol) and Xantphos (80 mg, 0.14 mmol) in 1,4- dioxane (20 mL) was stirred at 120°C for 16 hours. The reaction solution was poured into water (50 mL) and extracted with EtAOc (50 mL × 2). The organic layers were washed with brine (50 mL× 2), dried over Na2SO4 and concentrated. The residue was purified by prep-TLC (30% EtOAc in petroleum ether) to afford the title compound (50 mg, 16%) as a colorless oil. LCMS (ESI): m/z 370.1 (M+H) ⁺ . [0719] Step 6: (E)-4-(2-(4,4-Difluorocyclohexyl)vinyl)-5-methoxypyrimidin-2 -amine [0720] To a mixture of (E)-tert-butyl (4-(2-(4,4-difluorocyclohexyl)vinyl)-5- methoxypyrimidin- 2-yl)carbamate (50 mg, 0.17 mmol) in DCM (3 mL) was added TFA (1 mL) at 0°C. The solution was stirred at 0°C for 3 hours. The reaction solution was concentrated to afford the crude title compound (40 mg, 86%) as a brown oil. ¹ H NMR (400MHz, CDCl3): δ 7.97 (s, 1H), 7.04 - 7.00 (m, 1H), 6.71 (d, J = 15.6 Hz, 1H), 4.70 (s, 2H), 3.83 (s, 3H), 2.40 - 2.35 (m, 1H), 2.22 - 2.15 (m, 2H), 1.95 - 1.92 (m, 2H), 1.90 - 1.56 (m, 4H); LCMS (ESI): m/z 270.1 (M+H) ⁺ . [0721] Step 7: (E)-N-Acryloyl-N-(4-(2-(4,4-difluorocyclohexyl)vinyl)-5- methoxypyrimidin-2-yl)acrylamide [0722] To a mixture of (E)-4-(2-(4,4-difluorocyclohexyl)vinyl)-5-methoxypyrimidin-2 - amine (30 mg, 0.11 mmol) and TEA (0.05 mL, 0.33 mmol) in DCM (7.5 mL) was added acryloyl chloride (31 mg, 0.33 mmol) at 0°C. The reaction solution was stirred for 2 hours. The reaction solution was poured into water (30 mL) and extracted with DCM (30 mL × 2). The organic layers were dried over Na ₂ SO ₄ and concentrated to afford the crude title compound (20 mg, 48%) as a brown solid for next step directly. LCMS (ESI): m/z 378.1 (M+H) ⁺ . [0723] Step 8: (E)-N-(4-(2-(4,4-Difluorocyclohexyl)vinyl)-5-methoxypyrimidi n-2- yl)acrylamide [0724] To a mixture of (E)-N-acryloyl-N-(4-(2-(4,4-difluorocyclohexyl)vinyl)-5- methoxypyrimidin -2-yl)acrylamide (20 mg, 0.05 mmol) in THF (2 mL) was added a solution of sodium hydroxide (2.0 M, 3.0 mL, 6.0 mmol) at 0°C. The reaction mixture was stirred at 0°C for 1 hour. The reaction mixture was diluted by water (10 mL), extracted with EtOAc (10 mL × 2). The organic layers were combined, dried over Na ₂ SO ₄ and concentrated. The residue was purified by prep-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 40/70) to afford the title compound (2.11 mg, 12%) as a white solid. ¹ H NMR (400MHz, CDCl3): δ ^ ^ ^ ^ ^ ^ ^s, 1H ^ ^ ^ ^ ^ ^ ^ ^ ^s, 1H ^ ^ ^7.15 - 7.10 (m, 1H), 6.79 - 6.70 (m, 2H), 6.50 (d, J = 16.8 Hz, 1H), 5.86 - 5.82 (m, 1H), ^ ^ ^ ^ ^ ^s, 3H ^ ^ 2.40 - 2.35 (m, 1H), 2.22 - 2.15 (m, 2H), 1.95 - 1.92 (m, 2H), 1.90 - 1.56 (m, 4H); LCMS (ESI): m/z 324.1 (M+H) ⁺ . EXAMPLE 28 [0725] Preparation of 3-Acrylamido-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl) [0726] The overall reaction scheme was as follows: [0727] Step 1: 3-Amino-6-methoxy-5-((E)-2-(trans-4-(trifluoromethyl)cyclohe xyl)vinyl) picolinamide [0728] To a solution of 3-amino-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl) vinyl)picolinonitrile (100 mg, 0.31 mmol) in MeOH (10 mL) and DMSO (1 mL) was added NaOH (139 mg, 1.23 mmol), H2O2 (0.15 mL, 0.15 mmol). The mixture was stirred at 60°C for 2 hours. The resulting solution was extracted with EtOAc (50 mL × 2) and the organic layers were combined. The organic layer was dried over Na ₂ SO ₄ and concentrated to afford the title compound (90 mg, 85%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.60 (s, 1H), 7.07 (s, 1H), 6.50 (d, J = 16.0 Hz, 1H), 6.26 (dd, J = 16.0, 7.2 Hz, 1H), 5.57 (s, 2H), 5.31 (s, 1H), 3.90 (s, 3H), 2.23 - 2.10 (m, 1H), 2.03 - 1.92 (m, 5H), 1.47 - 1.35 (m, 2H), 1.25 - 1.14 (m, 2H). [0729] Step 2: 3-Acrylamido-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl) picolinamide [0730] To a mixture of 3-amino-6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl) picolinamide (90 mg, 0.26 mmol), TEA (0.07 mL, 0.52 mmol) in DCM (6 mL) was added acryloyl chloride (0.02 mL, 0.26 mmol) at -78°C. The mixture was stirred at -78°C for 1 hour. The reaction was quenched with water (20 mL). The resulting solution was extracted with DCM (30 mL × 2) and the organic layers were combined. The organic layer was dried over Na2SO4 and concentrated. The residue was purified pre-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 70/100) to afford the title compound (30.0 mg, 29%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 12.20 (s, 1H), 9.07 (s, 1H), 8.26 (s, 1H), 8.01 (s, 1H), 6.53 (d, J = 16.4 Hz, 1H), 6.42 - 6.31 (m, 2H), 6.25 (d, J = 16.8 Hz, 1H), 5.84 (dd, J = 10.8, 2.0 Hz, 1H), 3.97 (s, 3H), 2.31 - 2.14 (m, 2H), 1.98 - 1.82 (m, 4H), 1.42 - 1.19 (m, 4H). LCMS (ESI): m/z 398.1 (M+H) ⁺ . EXAMPLE 29 [0731] Preparation of (E)-N-(5-Cyano-4-(2-(4,4-difluorocyclohexyl)vinyl)pyridin-2- yl)acrylamide [0732] The overall reaction scheme was as follows:

[0733] Step 1: 6-Amino-4-chloronicotinonitrile [0734] To a solution of 4-chloro-5-iodopyridin-2-amine (500 mg, 1.96 mmol) in NMP (5 mL) was added Zn(CN)2 (127 mg, 1.08 mmol) and Pd(PPh3)4 (341 mg, 0.29 mmol). The mixture was stirred at 130°C for 5 hours under N ₂ . The mixture was diluted with water (100 mL) and the resultant mixture was extracted with EtOAc (20 mL × 3). The organic layer was brine (50 mL × 2), dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 50% ethyl acetate in petroleum ether) to afford the compound the title compound (240 mg, 80%) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 8.39 (s, 1H), 7.38 (s, 2H), 6.61 (s, 1H). [0735] Step 2: (E)-6-Amino-4-(2-(4,4-difluorocyclohexyl)vinyl)nicotinonitri le [0736] A mixture of (E)-2-(2-(4,4-difluorocyclohexyl)vinyl)-4,4,5,5-tetramethyl- 1,3,2- dioxaborolane (156 mg, 0.57 mmol), Xphos (25 mg, 0.05 mmol), K3PO4 (332 mg, 1.56 mmol), Pd(OAc) ₂ (12 mg, 0.05 mmol) and 6-amino-4-chloronicotinonitrile (80 mg, 0.52 mmol) in 1,4- dioxane (6 mL) and water (1.2 mL) was stirred at 100°C for 2 hours. The reaction mixture was diluted with water (40 mL). The resulting solution was extracted with ethyl acetate (40 mL × 2) and the organic layers were combined. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by pre-TLC (10% MeOH in DCM) to afford the title compound (60 mg, 44%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.33 (s, 1H), 6.61 - 6.53 (m, 2H), 6.46 (dd, J = 16.0, 7.2 Hz, 1H), 4.87 (s, 2H), 2.36 - 2.34 (m, 1H), 2.22 - 2.11 (m, 2H), 1.95 - 1.88 (m, 2H), 1.86 - 1.72 (m, 2H), 1.66 - 1.58 (m, 2H). [0737] Step 3: (E)-N-Acryloyl-N-(5-cyano-4-(2-(4,4-difluorocyclohexyl)vinyl )pyridin-2- yl) acrylamide [0738] To a mixture of (E)-6-amino-4-(2-(4,4-difluorocyclohexyl)vinyl)nicotinonitri le (45 mg, 0.17 mmol), DIPEA (0.06mL, 0.34 mmol) in DCM (4 mL) at -78°C was added acryloyl chloride (0.01mL, 0.17 mmol). The mixture was stirred at -78°C for 2 hours. The reaction mixture was diluted with water (20 mL). The resulting solution was extracted with DCM (20 mL × 2) and the organic layers were combined. The organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by pre-TLC (10% methanol in dichloromethane) to afford the title compound (50 mg, 79%) as a white solid. LCMS (ESI): m/z 372.1 (M+H) ⁺ . [0739] Step 4: (E)-N-(5-Cyano-4-(2-(4,4-difluorocyclohexyl)vinyl)pyridin-2- yl)acrylamide [0740] To a mixture of (E)-N-acryloyl-N-(5-cyano-4-(2-(4,4- difluorocyclohexyl)vinyl)pyridin-2-yl) acrylamide (50 mg, 0.13 mmol)) in THF (4 mL) was added a solution of sodium hydroxide (2.0 M, 2.0 mL, 6.0 mmol) stirred at 0°C for 30 minutes. The reaction was stirred at 0°C for 30 minutes. The reaction mixture was diluted by water (10 mL), extracted with EtOAc (10 mL × 2). The organic layers were combined, dried over Na ₂ SO ₄ and concentrated. The residue was purified pre-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 60/90) to afford the title compound (15.5 mg, 36%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.58 (s, 1H), 8.50 (s, 1H), 8.17 (s, 1H), 6.80 - 6.64 (m, 2H), 6.53 (d, J = 16.8 Hz, 1H), 6.29 (dd, J = 16.8, 10.4 Hz, 1H), 5.92 (d, J = 10.4 Hz, 1H), 2.44 - 2.31 (m, 1H), 2.24 - 2.12 (m, 2H), 1.97 - 1.88 (m, 2H), 1.88 - 1.72 (m, 2H), 1.70 - 1.64 (m, 2H). LCMS (ESI): m/z 318.1 (M+H) ⁺ . EXAMPLE 30 [0741] Preparation of 2-(((6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)amino)methyl) acrylic acid [0742] The overall reaction scheme was as follows: [0743] To a solution of DIPEA (0.42 mL, 2.5 mmol), 6-methoxy-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-amine (Intermediate D, 500 mg, 1.66 mmol) and 2- (((tert-butyldimethylsilyl)oxy)methyl)acrylic acid (1.0 g, 4.5 mmol) in DCM (20 mL) was added HATU (696 mg, 1.83 mmol) at room temperature. The reaction mixture was stirred for 30 minutes. The reaction mixture was quenched with water (50 mL), extracted with EtOAc (30 mL × 2). The organic layers were combined, dried over Na ₂ SO ₄ and concentrated. The resulting residue was purified by prep-HPLC (Boston Green ODS 150*30mm*5um, water (0.2%FA)-ACN, 52%-82%) to afford 30 mg crude product. The crude product was further purified by pre-TLC (10% MeOH in DCM) to afford the title compound (9.6 mg, 2%) as a white solid. ¹ H NMR (400 MHz, DMSO- d ₆ ): δ 7.35 (d, J = 2.8 Hz, 1H), 7.09 (d, J = 2.8 Hz, 1H), 6.40 (d, J = 16.0 Hz, 1H), 6.16 (dd, J = 16.0, 6.8 Hz, 1H), 5.89 ( s, 1H), 5.38 ( s, 1H), 3.82 (s, 2H), 3.74 (s, 3H), 2.24 - 2.20 (m, 1H), 2.14 - 2.10 (m, 1H), 1.90 - 1.80 (m, 4H), 1.33 - 1.20 (m, 4H). LCMS (ESI): m/z 385.2 (M+H) ⁺ . EXAMPLE 31 [0744] Preparation of 2-(((6-Cyano-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)amino)methyl) acrylic acid [0745] The overall reaction scheme was as follows: [0746] Step 1: 5-Amino-3-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)picolinonitrile [0747] A mixture of 4,4,5,5-tetramethyl-2-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)-1,3,2-dioxaborolane (396 mg, 1.3mmol), K3PO4 (829 mg, 3.91 mmol), Xphos Pd G ₃ (55 mg, 0.07 mmol), Xphos (31 mg, 0.07 mmol), 5-amino-3- chloropicolinonitrile (200 mg, 1.3 mmol) and in 1,4-dioxane (6 mL) and water (1 mL) was stirred at 100°C for 3 hours. The mixture was diluted with EtOAc (50 mL) and washed with water (30 mL). The organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 30% EtOAc in petroleum ether) to afford the title compound (350 mg, 91%) as a yellow solid. LCMS (ESI): m/z 296.1 (M+H) ⁺ . [0748] Step 2: 2-(((6-Cyano-5-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)pyridin-3-yl)amino)methyl) acrylic acid [0749] A mixture of DMAP (8 mg, 0.07 mmol), 5-amino-3-((E)-2-(trans-4- (trifluoromethyl)cyclohexyl)vinyl)picolinonitrile (200 mg, 0.68 mmol), 2-(((tert- butyldimethylsilyl)oxy)methyl)acrylic acid (439 mg, 2.03 mmol) and T3P (1.29 g, 2.03 mmol, 50% in ethyl acetate ) in ethyl acetate (3 mL) was stirred at 80°C for 16 hours. The mixture was quenched with water (100 mL) and extracted with EtOAc (100 mL × 2). The organic layer was washed with water (100 mL × 3), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (0 - 15 % EtOAc in petroleum ether) to afford 100 mg crude product. The crude product was further purified by pre-HPLC (3_Phenomenex Luna C1875*30mm*3um, water (0.2%FA)-ACN,60%-90%)to afford the title compound (27.5 mg, 11% ) as a white solid. ¹ H NMR (400 MHz,CDCl3): δ 7.95 (d, J = 2.4 Hz, 1H), 6.88 (d, J = 2.4 Hz, 1H), 6.63 (d, J = 16.0 Hz, 1H), 6.49 (s, 1H), 6.29 (dd, J = 16.0, 7.2 Hz, 1H), 5.92 (s, 1H), 4.73 (s, 1H), 4.14 (s, 2H), 2.28 - 2.18 (m, 1H), 2.10 - 1.97 (m, 5H), 1.51 - 1.34 (m, 2H), 1.32 - 1.14 (m, 2H). LCMS (ESI): m/z 380.2 (M+H) ⁺ . EXAMPLE 32 [0750] Preparation of (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-2,3- dihydrobenzofuran-5-yl)acrylamide [0751] The overall reaction scheme was as follows: [0752] Step 1: 7-Bromo-5-nitro-2,3-dihydrobenzofuran [0753] To an ice-cooled solution of 7-bromo-2,3-dihydrobenzofuran (2.0 g, 10.05 mmol) in TFA (20 mL) was added nitric acid (2.0 mL, 44.44 mmol) dropwise at 0°C. After 30 minutes, the ice bath was removed and the mixture was stirred at room temperature for 3 hours. The mixture was quenched with water (100 mL) and extracted with ethyl acetate (100 mL × 3). The organic layer was washed with water (100 mL × 3), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by column chromatography on silica gel (0 - 15% ethyl acetate in petroleum ether) to afford the title compound (2.0 g, 82%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.29 (d, J = 1.6 Hz, 1H), 8.04 (d, J = 1.6 Hz, 1H), 4.85 (t, J = 8.8 Hz, 2H), 3.43 (t, J = 8.8 Hz, 2H). [0754] Step 2: 7-Bromo-2 ,3-dihydrobenzofuran-5-amine [0755] To the solution of 7-bromo-5-nitro-2,3-dihydrobenzofuran (1.0 g, 4.1 mmol) in ethanol (10 mL) and water (2 mL) was added iron powder (2.3 g, 40.98 mmol) and NH4Cl (2.2 g, 40.98 mmol). The mixture was stirred at 80°C for 2 hours. The mixture was filtered, washed with ethanol (10 mL) and concentrated. The residue was dissolved in ethyl acetate (50 mL), washed with brine (20 mL × 3), dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (0 - 35% ethyl acetate in petroleum ether) to afford the title compound (770 mg, 88%) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d6): δ 6.49 (s, 1H), 6.47 (s, 1H), 4.76 (s, 2H), 4.43 (t, J = 8.8 Hz, 2H), 3.14 (t, J = 8.8 Hz, 2H). [0756] Step 3: (E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)-2,3-dihydrobenzofura n-5-amine [0757] A mixture of 7-bromo-2,3-dihydrobenzofuran-5-amine (200 mg, 0.93 mmol), (E)-2-(2-(4,4-difluorocyclohexyl)vinyl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (305 mg, 1.12 mmol), Pd(dppf)Cl2 (68 mg, 0.09 mmol) and K2CO3 (387 mg, 2.8 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was stirred at 100°C for 3 hours under N ₂ . The reaction mixture was concentrated under vacuum. The residue was purified by column chromatography on silica gel (0 - 30% ethyl acetate in petroleum ether) to afford the title compound (200 mg, 77%) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 6.38 (s, 1H), 6.35 (s, 1H), 6.26 (d, J = 16.4 Hz, 1H), 6.17 (dd, J = 16.4, 6.4 Hz, 1H), 4.49 (s, 2H), 4.40 (t, J = 8.8 Hz, 2H), 3.01 (t, J = 8.4 Hz, 2H), 2.30 - 2.20 (m, 1H), 2.08 - 1.96 (m, 2H), 1.95 - 1.77 (m, 4H), 1.44 - 1.31 (m, 2H). [0758] Step 4: (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-2,3-dihydrobenzof uran-5- yl)acrylamide [0759] To a mixture of (E)-7-(2-(4,4-difluorocyclohexyl)vinyl)-2,3-dihydrobenzofura n- 5-amine (150 mg, 0.54 mmol) and DIPEA (0.19 mL, 1.07 mmol) in DCM (3 mL) was added acryloyl chloride (0.04 mL, 0.48 mmol) at 0°C. The reaction was stirred at 0°C for 15 minutes. The reaction was quenched with water (20 mL). The mixture was extracted with DCM (30 mL × 2) and washed with water (10 mL × 3). The organic phase was dried over Na2SO4 and concentrated. The residue was purified by pre-HPLC (water (0.2%FA)-ACN, 55% - 85%) to afford the title compound (127.55 mg, 71%) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 9.96 (s, 1H), 7.43 (s, 1H), 7.40 (s, 1H), 6.43 - 6.18 (m, 4H), 5.69 (d, J = 2.4 Hz, 1H), 4.54 (t, J = 8.8 Hz, 2H), 3.15 (t, J = 8.8 Hz, 2H), 2.35 - 2.27 (m, 1H), 2.09 - 1.97 (m, 2H), 1.96 - 1.79 (m, 4H), 1.46 - 1.34 (m, 2H); LCMS (ESI): m/z 334.1 (M+H) ⁺ . EXAMPLE 33 [0760] Preparation of N-(7-(4-Isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)acrylami de [0761] The overall reaction scheme was as follows: [0762] Step 1: 7-(4-Isopropylphenyl)-2,3-dihydrobenzofuran-5-amine [0763] A mixture of 7-bromo-2,3-dihydrobenzofuran-5-amine (200 mg, 0.93 mmol), (4- isopropylphenyl)boronic acid (184 mg,1.12 mmol), Pd(dppf)Cl2 (68 mg, 0.09 mmol), K2CO3 (387 mg, 2.8 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was stirred at 100°C for 3 hours under N ₂ . The reaction mixture was concentrated under vacuum. The residue was purified by flash column chromatography on silica gel (0 - 30% ethyl acetate in petroleum ether) to afford the title compound (180 mg, 76%) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d6): δ 7.53 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 6.50 (s, 1H), 6.49 (s, 1H), 4.60 (s, 2H), 4.40 (t, J = 8.8 Hz, 2H), 3.08 (t, J = 8.8 Hz, 2H), 2.95 - 2.85 (m, 1H), 1.22 (d, J = 6.8 Hz, 6H). [0764] Step 2: N-(7-(4-Isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)acrylami de [0765] To a mixture of 7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-amine (180 mg, 0.71 mmol) and DIPEA (0.25 mL, 1.42 mmol) in DCM (3 mL) was added acryloyl chloride (0.05 mL, 0.64 mmol) at 0°C. The reaction was stirred at 0°C for 15 minutes. The reaction was quenched with water (20 mL). The mixture was extracted with DCM (30 mL × 2) and washed with water (20 mL × 3). The organic phase was dried over Na2SO4 and concentrated. The residue was purified by pre-HPLC (water (0.2%FA)-ACN, 60%~90%) to afford the title compound (93.51 mg, 42%) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.01 (s, 1H), 7.54 - 7.51 (m, 4H), 7.27 (d, J = 8.0 Hz, 2H), 6.42 (dd, J = 16.8, 10.0 Hz, 1H), 6.23 (dd, J = 16.8, 2.0 Hz, 1H), 5.71 (d, J = 10.0 Hz, 1H), 4.51 (t, J = 8.8 Hz, 2H), 3.19 (t, J = 8.8 Hz, 2H), 2.92 - 2.82 (m, 1H), 1.19 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 308.1 (M+H) ⁺ . EXAMPLE 34 [0766] Preparation of N-(7-(((trans-4-(Trifluoromethyl)cyclohexyl)oxy)methyl)-2,3- dihydrobenzofuran-5-yl)acrylamide [0767] The overall reaction scheme was as follows: [0769] A mixture of 7-bromo-2,3-dihydrobenzofuran (6.0 g, 30.14 mmol) and NCS (4.0 g, 30.14 mmol) in MeCN (60 mL) were stirred at 80°C for 16 hours. The mixture reaction was concentrated. The residual was purified by column chromatography on silica gel (0 - 5% EtOAc in petroleum ether) to afford the title compound (6.5 g, 92%) as a yellow oil. ¹ H NMR (400 MHz, CD ₃ OD): δ 7.25 (s, 1H), 7.17 (s, 1H), 4.64 (t, J = 8.8 Hz, 2H), 3.31 (t, J = 8.8 Hz, 2H). [0770] Step 2: 5-Chloro-2,3-dihydrobenzofuran-7-carbaldehyde [0771] To a stirred solution of 7-bromo-5-chloro-2,3-dihydrobenzofuran (3.0 g, 12.85 mmol) in dry THF(40 mL) was added n-BuLi (6.17 mL, 15.42 mmol, 2.5 M solution in hexane) in drops over 10 min at -78°C and stirred at same temperature for 1 hour. To this reaction mixture, DMF (2.97 mL, 38.55 mmol) was added at -78°C dropwise. The reaction mixture was stirred for 1 hour at -78°C. The reaction mixture was quenched with the addition of a saturated aqueous solution of NH ₄ Cl (20 mL) and extracted with ethyl acetate (50 mL × 3). The combined organic layers were concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (0 - 15% ethyl acetate in petroleum ether) to afford the title compound (1.5 g, 64%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 10.14 (s, 1H), 7.56 (d, J = 2.0 Hz, 1H), 7.36 (d, b = 2.0 Hz, 1H), 4.77 (t, J = 8.8 Hz, 2H), 3.26 (t, J = 8.8 Hz, 2H). [0772] Step 3: (5-Chloro-2,3-dihydrobenzofuran-7-yl)methanol [0773] To a stirred solution of 5-chloro-2,3-dihydrobenzofuran-7-carbaldehyde (1.5 g, 8.21 mmol) in MeOH (40 mL) was added NaBH4 (1.56 g, 41.07 mmol) at room temperature. The mixture was stirred at room temperature for 1 hour. The mixture was quenched with NH ₄ Cl solution (50 mL). Then water (50 mL) was added and the aqueous layer was extracted with EtOAc (100 mL × 2). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 20% EtOAc in petroleum ether) to afford the title compound (1.4 g, 92%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.10 (s, 1H), 7.10 (s, 1H), 4.65 - 4.60 (m, 4H), 3.21 (t, J = 8.8 Hz, 2H), 2.07 (t, J = 5.6 Hz, 1H). [0774] Step 4: 7-(Bromomethyl)-5-chloro-2,3-dihydrobenzofuran [0775] To the mixture of (5-chloro-2,3-dihydrobenzofuran-7-yl)methanol (700 mg, 3.79 mmol) in DCM (7 mL) was added PBr3 (0.14 mL, 1.52 mmol) at 0°C. The reaction was stirred at room temperature for 2 hours. The reaction was quenched with NaHCO ₃ solution (5 mL). The mixture was extracted with DCM (100 mL × 2) and washed with water (30 mL × 3). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (720 mg, 77%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.11 (s, 1H), 7.11 (s, 1H), 4.67 (t, J = 8.8 Hz, 2H), 4.42 (s, 2H), 3.22 (t, J = 8.8 Hz, 2H). [0776] Step 5: 5-Chloro-7-(((trans-4-(trifluoromethyl)cyclohexyl)oxy)methyl )-2,3- dihydrobenzofuran [0777] To a solution of trans-4-(trifluoromethyl)cyclohexanol (326 mg, 1.94 mmol) in DMF (5 mL) was added NaH (60% in mineral oil, 78 mg, 3.23 mmol) at 0 ^o C. After the mixture was stirred at 0°C for 30 minutes. Then 7-(bromomethyl)-5-chloro-2,3-dihydrobenzofuran (400 mg, 1.62 mmol) was added and the mixture was stirred at 60°C for 30 minutes. The mixture was quenched with water (10 mL), diluted with EtOAc (100 mL × 2) and washed with water (100 mL × 2). The organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 5% ethyl acetate in petroleum ether) to afford the title compound (450 mg, 83%) as a colorless liquid. ¹ H NMR (400 MHz, CDCl3): δ 7.15 (s, 1H), 7.08 (s, 1H), 4.60 (t, J = 8.8 Hz, 2H), 4.49 (s, 2H), 3.37 - 3.29 (m, 1H), 3.20 (t, J = 8.8 Hz, 2H), 2.24 - 2.17 (m, 2H), 2.04 - 1.97 (m, 3H), 1.42 - 1.29 (m, 4H). [0778] Step 6: 7-(((trans-4-(Trifluoromethyl)cyclohexyl)oxy)methyl)-2,3- dihydrobenzofuran-5-amine [0779] A solution of 5-chloro-7-(((trans-4-(trifluoromethyl)cyclohexyl)oxy)methyl )-2,3- dihydrobenzofuran (450 mg, 1.34 mmol), CuI (26 mg, 0.13 mmol), NH ₃ ^. H ₂ O (0.49 mL, 4.03 mmol), N ¹ ,N ² -bis(5-methyl-[1,1'-biphenyl]-2-yl)oxalamide (57 mg, 0.13 mmol) and K3PO4 (856 mg, 4.03 mmol) in DMSO (5 mL) was stirred at 120°C for 3 hours. The reaction mixture was diluted with EtOAc (100 mL) and washed with brine (100 mL × 2). The organic layers were dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 50% EtOAc in petroleum ether) to afford the title compound (170 mg, 40%) as a brown oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.55 (s, 1H), 6.55 (s, 1H), 4.54 - 4.47 (m, 4H), 3.48 - 3.28 (m, 3H), 3.13 (t, J = 8.4 Hz, 2H), 2.25 - 2.15 (m, 2H), 2.05 - 1.95 (m, 3H), 1.43 - 1.28 (m, 4H); LCMS (ESI): m/z 316.1 (M+H) ⁺ . [0780] Step 7: N-(7-(((trans-4-(Trifluoromethyl)cyclohexyl)oxy)methyl)-2,3- dihydrobenzofuran-5-yl)acrylamide [0781] A solution of 7-(((trans-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-2,3- dihydrobenzofuran-5-amine (170 mg, 0.54 mmol), DIPEA (70 mg, 0.54 mmol) in DCM (4 mL) was stirred at 0°C for 15 minutes. Then acryloyl chloride (59 mg, 0.65 mmol) was added into it and the mixture was stirred at 0°C for 30 minutes. The reaction mixture was diluted with water (30 mL), and extracted with DCM (30 mL × 2). The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by HPLC (3_Phenomenex Luna C18 75*30mm*3um, water (0.2%FA)-ACN, 60-90%) to afford the title compound (99.85 mg, 50%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 7.57 ( s, 1H), 7.35 (s, 1H), 7.14 ( s, 1H), 6.40 ( d, J = 16.8 Hz, 1H), 6.22 (dd, J = 16.8, 10.4 Hz, 1H), 5.73 (d, J = 10.4 Hz, 1H), 4.58 (t, J = 8.8 Hz, 2H), 4.51 (s, 2H), 3.40 - 3.28 (m, 1H), 3.20 ( t, J = 8.8 Hz, 2H), 2.25 - 2.15 (m, 2H), 2.04 - 1.95 (m, 3H), 1.39 - 1.26 (m, 4H); LCMS (ESI): m/z 370.1 (M+H) ⁺ . EXAMPLE 35 [0782] Preparation of (R,E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-2-methyl-2,3- dihydrobenzofuran-5-yl)acrylamide and (S,E)-N-(7-(2-(4,4-difluorocyclohexyl)vinyl)-2-methyl- 2,3-dihydrobenzofuran-5-yl)acrylamide [0783] The overall reaction scheme was as follows:

[0785] To a mixture of 2-bromophenol (25.0 g, 144.5 mmol) and Cs ₂ CO ₃ (94.0 g, 289 mmol) in acetonitrile (250 mL) was added 3-bromoprop-1-ene (21.0 g, 173.4 mmol). The mixture was stirred at room temperature for 3 hours. The reaction was quenched with water (500 mL) and diluted with EtOAc (1.0 L), washed with water (500 mL × 2). The organic layer was dried over Na ₂ SO ₄ and evaporated in vacuum to afford the title compound (30.0 g, 97%) as a colorless liquid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.60 - 7.48 (m, 1H), 7.29 - 7.19 (m, 1H), 6.95 - 6.78 (m, 2H), 6.13 - 6.01 (m, 1H), 5.56 - 5.44 (m, 1H), 5.36 - 5.25 (m, 1H), 4.66 - 4.57 (m, 2H). [0786] Step 2: 2-Allyl-6-bromophenol [0787] To a mixture of 1-(allyloxy)-2-bromobenzene (10.0 g, 46.93 mmol) in hexane (100 mL) was added diethylaluminum chloride (46.93 mL, 46.93 mmol, 1.0 M solution in hexane) at room temperature. The mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with water (100 mL), diluted with EtOAc (300 mL) and washed with water (150 mL × 2). The organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (100% petroleum ether) to afford the title compound (7.0 g, 70%) as a colorless liquid. ¹ H NMR (400 MHz, CDCl3): δ 7.34 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 6.77 (t, J = 7.6 Hz, 1H), 6.08 - 5.93 (m, 1H), 5.60 (s, 1H), 5.14 - 5.11 (m, 1H), 5.10 - 5.07 (m, 1H), 3.45 (d, J = 6.4 Hz, 2H). [0788] Step 3: 7-Bromo-2-methyl-2,3-dihydrobenzofuran [0789] A solution of 2-allyl-6-bromophenol (5.0 g, 23.47 mmol), and Al(OTf) ₃ (556 mg, 1.17 mmol) in CH ₃ NO ₂ (80 mL) was stirred at 100°C for 3 hours. The mixture was quenched with water (100 mL) and extracted with EtOAC (100 mL × 3). The organic layer was washed with water (100 mL × 3), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (100% petroleum ether) to afford the title compound (2.0 g, 40%) as a colorless liquid. ¹ H NMR (400 MHz, CDCl3): δ 7.26 (d, J = 7.2 Hz, 1H), 7.08 (d, J = 7.2 Hz, 1H), 6.71 (t, J = 7.6 Hz, 1H), 5.10 - 4.95 (m, 1H), 3.41 (dd, J = 15.6, 8.8 Hz, 1H), 2.92 (dd, J = 15.6, 8.0 Hz, 1H), 1.52 (d, J = 6.0 Hz, 3H). [0790] Step 4: 7-Bromo-2-methyl-5-nitro-2,3-dihydrobenzofuran [0791] To an ice-cooled solution of 7-bromo-2-methyl-2,3-dihydrobenzofuran (1.0 g, 4.69 mmol) in TFA (10 mL) was added nitric acid (0.65 mL, 9.39 mmol) dropwise at 0°C. After 30 minutes, the ice bath was removed and the mixture was stirred at room temperature for 3 hours. The mixture was quenched with water (100 mL) and extracted with EtOAC (100 mL × 3). The organic layer was washed with water (100 mL × 3), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (0 - 15 % EtOAc in petroleum ether) to afford the title compound (1.0 g, 83%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 1.2 Hz, 1H), 8.01 (d, J = 1.2 Hz, 1H), 5.28 - 5.15 (m, 1H), 3.52 (dd, J = 16.0, 9.2 Hz, 1H), 3.01 (dd, J = 16.0, 7.6 Hz, 1H), 1.58 (d, J = 5.6 Hz, 3H). [0792] Step 5: 7-Bromo-2-methyl-2,3-dihydrobenzofuran-5-amine [0793] To a solution of 7-bromo-2-methyl-5-nitro-2,3-dihydrobenzofuran (1.0 g, 3.87 mmol) in ethanol (5 mL) and water (5 mL) was added iron (2.2 g, 38.75 mmol) and NH ₄ Cl (2.1 g, 38.75 mmol). The mixture was stirred at 80°C for 2 hours. The mixture was filtered, washed with ethanol (10 mL) and concentrated. The residue was dissolved in ethyl acetate (50 mL), washed with brine (30 mL × 3). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (0 - 35% ethyl acetate in petroleum ether) to afford the title compound (850 mg, 96%) as a yellow liquid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.64 (d, J = 1.2 Hz, 1H), 6.49 (d, J = 1.2 Hz, 1H), 5.01 - 4.87 (m, 1H), 3.49, (s, 2H), 3.33 (dd, J = 15.6, 8.0 Hz, 1H), 2.83 (dd, J = 15.6, 8.0 Hz, 1H), 1.49 (d, J = 6.0 Hz, 3H). [0794] Step 6: (E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)-2-methyl-2,3- dihydrobenzofuran-5-amine [0795] A mixture of 7-bromo-2-methyl-2,3-dihydrobenzofuran-5-amine (400 mg, 1.75 mmol), (E)-2-(2-(4,4-difluorocyclohexyl)vinyl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (573 mg, 2.1 mmol), Pd(dppf)Cl ₂ (128 mg, 0.18 mmol), K ₂ CO ₃ (727 mg, 5.26 mmol) in 1,4-dioxane (8 mL) and water (2 mL) was stirred at 100°C for 3 hours under N2. The reaction mixture was concentrated under vacuum. The residue was purified by column chromatography on silica gel (0 - 30% ethyl acetate in petroleum ether) to afford the title compound (450 mg, 87%) as a yellow liquid. ¹ H NMR (400 MHz, CDCl3): δ 6.50 (d, J = 2.4 Hz, 1H), 6.46 (d, J = 2.4 Hz, 1H), 6.39 (d, J = 16.0 Hz, 1H), 6.24 (dd, J = 16.0, 6.4 Hz, 1H), 4.93 - 4.81 (m, 1H), 3.36 (s, 2H), 3.20 (dd, J = 15.6, 8.0 Hz, 1H), 2.73 (dd, J = 15.6, 8.0 Hz, 1H), 2.28 - 2.18 (m, 1H), 2.17 - 2.07 (m, 2H), 1.96 - 1.69 (m, 4H), 1.56 - 1.50 (m, 2H), 1.46 (d, J = 6.4 Hz, 3H). [0796] Step 7: (R,E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)-2-methyl-2,3- dihydrobenzofuran-5-amine and (S,E)-7-(2-(4,4-difluorocyclohexyl)vinyl)-2-methyl-2,3- dihydrobenzofuran-5-amine [0797] (E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)-2-methyl-2,3-dihydro benzofuran-5- amine (450 mg, 1.53 mmol) was separated by SFC (daicel chiralpak ad-h(250mm*30mm,5um), 0.1% NH ₃ ^. H ₂ O MeOH, 40%-40%) to afford (R,E)-7-(2-(4,4-difluorocyclohexyl)vinyl)-2-methyl- 2,3-dihydrobenzofuran-5-amine as a colorless oil and (S,E)-7-(2-(4,4-difluorocyclohexyl)vinyl)- 2-methyl-2,3-dihydrobenzofuran-5-amine as a colorless oil. First eluent from SFC = Enantiomer A (180 mg, 40%) and the second eluent from SFC = Enantiomer B (180 mg, 40%). [0798] Step 8: (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-2-methyl-2,3- dihydrobenzofuran-5-yl)acrylamide, Enantiomer C [0799] A solution of Enantiomer A (180 mg, 0.61 mmol) and DIPEA (79 mg, 0.61 mmol) in DCM (2 mL) was stirred at room temperature for 5 minutes. Then acryloyl chloride (56 mg, 0.61 mmol) was added into it at 0°C. The mixture was stirred at 0°C for 15 minutes. The reaction mixture was diluted with water (30 mL), and extracted with DCM (30 mL × 2). The combined organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by pre-HPLC (Boston Green ODS 150*30mm*5um, water (0.2%FA)-ACN, 62-92%) to afford the title compound, Enantiomer C, (144.3 mg, 67%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.35 (s, 1H), 7.23 (s, 1H), 7.16 (s, 1H), 6.46 - 6.37 (m, 2H), 6.35 - 6.27 (m, 1H), 6.22 (dd, J = 16.8, 10.0 Hz, 1H), 5.75 (d, J = 10.0 Hz, 1H), 5.03 - 4.90 (m, 1H), 3.29 (dd, J = 15.6, 8.8 Hz, 1H), 2.80 (dd, J = 15.6, 8.0 Hz, 1H), 2.30 - 2.20 (m, 1H), 2.17 - 2.08 (m, 2H), 1.92 - 1.70 (m, 4H), 1.58 - 1.50 (m, 2H), 1.48 (d, J = 6.4 Hz, 3H); LCMS (ESI): m/z 348.1 (M+H) ⁺ . [0800] Step 9: (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-2-methyl-2,3- dihydrobenzofuran-5-yl)acrylamide, Enantiomer D [0801] A solution of DIPEA (79.3 mg, 0.61 mmol) and Enantiomer B (180 mg, 0.61 mmol) in DCM (2 mL) was stirred at room temperature for 5 minutes, then acryloyl chloride (56 mg, 0.61 mmol) was added into it at 0°C. The mixture was stirred at 0°C for 2 hours. The reaction mixture was diluted with water (30 mL), and extracted with DCM (30 mL × 2). The combined organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by pre-HPLC (Boston Green ODS 150*30mm*5um, water (0.2%FA)-ACN, 62-92%) to afford the title compound, Enantiomer D, (128.46 mg, 60%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.35 (s, 1H), 7.23 (s, 1H), 7.16 (s, 1H), 6.46 - 6.37 (m, 2H), 6.34 - 6.27 (m, 1H), 6.22 (dd, J = 16.8, 10.0 Hz, 1H), 5.75 (d, J = 10.0 Hz, 1H), 5.01 - 4.90 (m, 1H), 3.29 (dd, J = 15.6, 8.8 Hz, 1H), 2.80 (dd, J = 15.6, 8.0 Hz, 1H), 2.30 - 2.20 (m, 1H), 2.18 - 2.07 (m, 2H), 1.91 - 1.69 (m, 4H), 1.58 - 1.51 (m, 2H), 1.48 (d, J = 6.4 Hz, 3H); LCMS (ESI): m/z 348.1 (M+H) ⁺ . EXAMPLE 36 [0802] Preparation of (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-2,3- dihydrobenzofuran-5-yl)-N-(2-hydroxyethyl)acrylamide [0803] The overall reaction scheme was as follows: [0804] Step 1: (E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)-2,3-dihydrobenzofura n-5-amine [0805] A mixture of 7-bromo-2,3-dihydrobenzofuran-5-amine (300 mg, 1.4 mmol), 2- [(E)-2-(4,4-difluorocyclohexyl)vinyl]-4,4,5,5-tetramethyl-1, 3,2-dioxaborolane (458 mg, 1.7 mmol), Pd(dppf)Cl ₂ (102 mg, 0.14 mmol), K ₂ CO ₃ (581 mg, 4.2 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was stirred at 100°C for 3 hours under N2. The reaction mixture was concentrated under vacuum. The residue was purified by flash column chromatography on silica gel (0 - 30% ethyl acetate in petroleum ether) to afford the title compound (350 mg, 89%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.49 (s, 1H), 6.49 (s, 1H), 6.37 (d, J = 16.0 Hz, 1H), 6.28 (dd, J = 16.0 Hz, 6.8 Hz, 1H), 4.54 (t, J = 8.8 Hz, 2H), 3.12 (t, J = 8.8 Hz, 2H), 2.24 - 2.20 (m, 1H), 2.11 - 2.10 (m, 2H), 1.99 - 1.89 (m, 2H), 1.85 - 1.69 (m, 4H). LCMS (ESI): m/z 280.2 (M+H) ⁺ . [0806] Step 2: (E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)-N-(2-((tetrahydro-2H -pyran-2- yl)oxy)ethyl)-2,3-dihydrobenzofuran-5-amine [0807] A reaction mixture of 2-(2-bromoethoxy)tetrahydro-2H-pyran (150 mg, 0.72 mmol), potassium carbonate (198 mg, 1.43 mmol), sodium iodide (107 mg, 0.72 mmol) and (E)- 7-(2-(4,4-difluorocyclohexyl)vinyl)-2,3-dihydrobenzofuran-5- amine (200 mg, 0.72 mmol) in DMF (3 mL) was stirred at 60°C for 16 hours. Then it was quenched with H ₂ O (20 mL). The resulting solution was extracted with EtOAc (50 mL × 2), washed with H ₂ O (20 mL × 2). The organic layers were dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 17 % EtOAc in petroleum ether) to afford the title compound (200 mg, 68%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.49 (s, 1H), 6.44 (s, 1H), 6.39 (d, J = 16.0 Hz, 1H), 6.29 (dd, J = 16.0 Hz, 6.8 Hz, 1H), 4.64 - 4.60 (m, 1H), 4.54 (t, J = 8.8 Hz, 2H), 3.96 - 3.86 (m, 2H), 3.69 - 3.65 (m, 1H), 3.55 - 3.50 (m, 1H), 3.29 - 3.26 (m, 2H), 3.14 (t, J = 8.8 Hz, 2H), 2.24 - 2.20 (m, 1H), 2.14 - 2.10 (m, 2H), 1.93 - 1.65 (m, 10H), 1.35 - 1.22 (m, 2H); LCMS (ESI): m/z 408.3 (M+H) ⁺ . [0808] Step 3: (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-2,3-dihydrobenzof uran-5- yl)-N-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)acrylamide [0809] To a mixture of (E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)-N-(2-((tetrahydro-2H - pyran-2-yl)oxy)ethyl)-2,3-dihydrobenzofuran-5-amine (100 mg, 0.25 mmol) and TEA (0.04 mL, 0.27 mmol) in DCM (2 mL) was added acryloyl chloride (0.02 mL, 0.25 mmol) dropwise at 0°C under N ₂ . The reaction mixture was diluted with water (40 mL), and extracted with DCM (40 mL × 2). The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by pre-TLC (30 % EtOAc in petroleum ether) to afford the title compound (70 mg, 62%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.98 (s, 1H), 6.90 (s, 1H), 6.40 - 6.27 (m, 3H), 6.14 - 6.04 (m, 1H), 5.50 (dd, J = 10.4, 2.0 Hz, 1H), 4.67 (t, J = 8.8 Hz, 2H), 4.61 - 4.58 (m, 1H), 4.03 - 4.00 (m, 1H), 3.94 - 3.76 (m, 3H), 3.73 - 3.60 (m, 1H), 3.54 - 3.41 (m, 1H), 3.21 (t, J = 8.8 Hz, 2H), 2.26 - 2.24 (m, 1H), 2.19 - 2.05 (m, 2H), 1.92 - 1.67 (m, 10H), 1.54 - 1.44 (m, 2H). LCMS (ESI): m/z 485.2 (M+Na) ⁺ . [0810] Step 4: (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-2,3-dihydrobenzof uran-5-yl)- N- (2-hydroxyethyl)acrylamide [0811] The solution of (E)-N-(7-(2-(4,4-difluorocyclohexyl)vinyl)-2,3- dihydrobenzofuran-5-yl)-N-(2-((tetrahydro-2H-pyran-2-yl)oxy) ethyl)acrylamide (65 mg, 0.14 mmol) in THF (3 mL) and solution HCl (1 mL, 1 mmol) was stirred at room temperature for 2 hours. The mixture was diluted with water (20 mL), extracted with EtOAc (20 mL × 2). Combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by pre-TLC (50 % EtOAc in petroleum ether) to afford the title compound (36 mg, 68%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.93 (s, 1H), 6.89 (s, 1H), 6.47 - 6.29 (m, 3H), 6.09 (dd, J =16.8, 10.4 Hz, 1H), 5.56 (dd, J = 10.4, 2.0 Hz, 1H), 4.68 (t, J = 8.8 Hz, 2H), 3.97 - 3.89 (m, 2H), 3.83 - 3.80 (m, 2H), 3.43 ( s, 1H), 3.23 (t, J = 8.8 Hz, 2H), 2.26 - 2.24 (m, 1H), 2.19 - 2.05 (m, 2H), 1.90 - 1.76 (m, 4H), 1.65 - 1.50 (m, 2H). LCMS (ESI): m/z 378.1 (M+H) ⁺ . EXAMPLE 37 [0812] Preparation of (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-4-fluoro-2,3- dihydrobenzofuran-5-yl)acrylamide [0813] The overall reaction scheme was as follows: [0814] Step 1: 1-Chloro-2-(2,2-diethoxyethoxy)-4-fluorobenzene [0815] A reaction mixture of 2-chloro-5-fluorophenol (20.0 g, 136 mmol), K ₂ CO ₃ (28.3 g, 204 mmol), 2-bromo-1,1-diethoxyethane (29.6 g, 150 mmol) in DMF (200 mL) was stirred at 135°C for 16 hours. The reaction mixture was concentrated and diluted with EtOAc (600 mL), washed with brine (500 mL × 5). The organic layers were combined, dried over Na ₂ SO ₄ , filtered and concentrated to afford the title compound (31 g, 86%) as a colorless oil. ¹ H NMR (400 MHz, CDCl3): δ 7.30 - 7.23 (m, 1H), 6.67 (dd, J = 10.0, 2.4 Hz, 1H), 6.64 - 6.56 (m, 1H), 4.85 (t, J = 5.2 Hz, 1H), 4.01 (d, J = 5.2 Hz, 2H), 3.79 - 3.76 (m, 2H), 3.68 - 3.66 (m, 2H), 1.26 - 1.20 (m, 6H). [0816] Step 2: 7-Chloro-4-fluorobenzofuran [0817] A reaction mixture of 1-chloro-2-(2,2-diethoxyethoxy)-4-fluorobenzene (30.0 g, 114 mmol) and PPA (30.0 g) in toluene (500 mL) was stirred at 110°C for 5 hours. The reaction mixture was quenched with aq. NaHCO3 (800 mL), extracted with EtOAc (1 L × 3). Combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by column chromatography on silica gel (100% petroleum ether) to afford the title compound (9.0 g, 46%) as a colorless oil. ¹ H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 2.4 Hz, 1H), 7.30 (dd, J = 8.0, 2.4 Hz, 1H), 7.00 - 6.91 (m, 2H). [0818] Step 3: 7-Chloro-4-fluoro-2,3-dihydrobenzofuran [0819] A reaction mixture of 7-chloro-4-fluorobenzofuran (9.0 g, 52.0 mmol) and 10% Rh/C (5.0 g, 4.86 mmol) in ethanol (120 mL) was stirred under H ₂ (15 psi) for 2 hours. The reaction mixture was filtered and the filtrate was concentrated. The residue was purified by column chromatography on silica gel (0 - 5 % EtOAc in petroleum ether) to afford the title compound (6.0 g, 66%) as a colorless oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.08 (dd, J = 8.4, 5.2 Hz, 1H), 6.53 (t, J = 8.4 Hz 1H), 4.73 (t, J = 8.8 Hz, 2H), 3.33 (t, J = 8.8 Hz, 2H). [0820] Step 4: 7-Chloro-4-fluoro-5-nitro-2,3-dihydrobenzofuran [0821] To an ice-cooled solution of 7-chloro-4-fluoro-2,3-dihydrobenzofuran (200 mg, 1.16 mmol) in TFA (2 mL) was added nitric acid (0.18 mL, 2.67 mmol) dropwise at 0°C. After 30 minutes, the ice bath was removed and the mixture was stirred at room temperature for 3 hours. The mixture was quenched with water (50 mL) and extracted with EtOAc (50 mL × 3). Combined organic layers were washed with water (100 mL × 3), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by pre-TLC (10% EtOAc in petroleum ether) to afford the title compound (200 mg, 82%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 6.8 Hz, 1H), 4.89 (t, J = 8.8 Hz, 2H), 3.43 (t, J = 8.8 Hz, 2H). [0822] Step 5: 7-Chloro-4-fluoro-2,3-dihydrobenzofuran-5-amine [0823] To a mixture of 7-chloro-4-fluoro-5-nitro-2,3-dihydrobenzofuran (200 mg, 0.92 mmol) and NH ₄ Cl (490 mg, 9.19 mmol) in THF (2 mL) and water (1 mL) was added iron (260 mg, 4.60 mmol). The mixture was stirred under N2 at 80°C for 2 hours. The mixture was filtered. The filtrate was diluted with water (50 mL), extracted with EtOAc (50 mL × 2). Combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by pre-TLC (30% ethyl acetate in petroleum ether) to afford the title compound (160 mg, 93%) as a brown solid. ¹ H NMR (400 MHz, CDCl3): δ 6.59 (d, J = 8.0 Hz, 1H), 4.65 (t, J = 8.8 Hz, 2H), 3.45 (s, 2H), 3.30 (t, J = 8.8 Hz, 2H). [0824] Step 6: (E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)-4-fluoro-2,3-dihydro benzofuran- 5-amine [0825] A solution of (E)-2-(2-(4,4-difluorocyclohexyl)vinyl)-4,4,5,5-tetramethyl- 1,3,2- dioxaborolane (232 mg, 0.85 mmol), Xphos Pd G3 (36 mg, 0.04 mmol), Xphos (20 mg, 0.04 mmol), K ₃ PO ₄ (543 mg, 2.56 mmol) and 7-chloro-4-fluoro-2,3-dihydrobenzofuran-5-amine (160 mg, 0.85 mmol) in 1,4-dioxane (3 mL) and water (0.5 mL) was stirred at 80°C for 5 hours. The reaction mixture was quenched with water (50 mL) and extracted with EtOAc (50 mL × 2). The organic layer was washed with water (50 mL). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (150 mg, 59%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.58 (d, J = 8.8 Hz, 1H), 6.32 (d, J = 16.0 Hz 1H), 6.19 (dd, J = 16.0 Hz, 6.8 Hz 1H), 4.60 (t, J = 8.8 Hz 2H), 3.38 (s, 2H), 3.21 (t, J = 8.8 Hz, 2H), 2.27 - 2.17 (m, 1H), 2.16 - 2.07 (m, 2H), 1.92 - 1.67 (m, 4H), 1.57 - 1.48 (m, 2H). [0826] Step 7: (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)-4-fluoro-2,3- dihydrobenzofuran-5-yl) acrylamide [0827] To the mixture of TEA (0.11 mL, 0.76 mmol) and (E)-7-(2-(4,4- difluorocyclohexyl)vinyl)-4-fluoro-2,3-dihydrobenzofuran-5-a mine (150 mg, 0.50 mmol) in DCM (3 mL) was added acryloyl chloride (0.041 mL, 0.55 mmol). The reaction was stirred at - 78°C under N2 for 4 hours. The reaction mixture was quenched with water (10 mL), extracted with DCM (50 mL × 2). The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by pre-HPLC (Phenomenex Luna C1875*30mm*3um, water (0.2%FA)-ACN, 59-89%) to afford the title compound (108 mg, 61% ) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 9.72 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 6.51 (dd, J = 17.2, 10.0 Hz, 1H), 6.41 - 6.16 (m, 3H), 5.74 (dd, J = 10.0, 2.0 Hz, 1H), 4.67 (t, J = 8.8 Hz, 2H), 3.24 (t, J = 8.8 Hz, 2H), 2.31 - 2.96 (m, 1H), 2.07 - 1.98 (m, 2H), 1.96 - 1.77 (m, 4H), 1.48 - 1.31 (m, 2H). LCMS (ESI): m/z 352.2 (M+H) ⁺ . EXAMPLE 38 [0828] Preparation of N-(5-((trans-4-(Trifluoromethyl)cyclohexyl)oxy)quinolin-3- yl)acrylamide [0829] The overall reaction scheme was as follows:

[0830] Step 1: 5-((trans-4-(Trifluoromethyl)cyclohexyl)oxy)quinolone [0831] A mixture of quinolin-5-ol (1.0 g, 6.89 mmol), cis-4- (trifluoromethyl)cyclohexanol (1.2 g, 6.89 mmol), PPh ₃ (3.6 g, 13.78 mmol) in THF (15 mL) at 0°C was stirred for 5 minutes, then DIAD (2.8 g, 13.78 mmol) was added into the mixture at 0°C. The mixture was stirred at room temperature for 12 hours. Then the reaction mixture was diluted with water (50 mL). The resulting solution was extracted with ethyl acetate (50 mL × 2) and the organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 20% ethyl acetate in petroleum ether) to afford the title compound (340 mg, 17%) as a colorless oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.91 (dd, J = 4.4, 2.0 Hz, 1H), 8.57 (dd, J = 8.4, 1.2 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.38 (dd, J = 8.4, 4.4 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H), 4.54 - 4.35 (m, 1H), 2.44 - 2.36 (m, 2H), 2.21 - 2.08 (m, 3H), 1.59 - 1.50 (m, 2H), 1.35 - 1.23 (m, 2H). [0832] Step 2: 5-((trans-4-(Trifluoromethyl)cyclohexyl)oxy)quinoline 1-oxide [0833] A mixture of m-CPBA (273 mg, 1.27 mmol, 85% wt) and 5-((trans-4- (trifluoromethyl)cyclohexyl)oxy)quinoline (340 mg, 1.15 mmol) in DCM (5 mL) was stirred at room temperature for 16 hours. The reaction was quenched with saturated aqueous NaHCO3 (10 mL). The resulting solution was extracted with dichloromethane (40 mL × 2) and the organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 10% methanol in dichloromethane) to afford the title compound (320 mg, 89%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 8.53 (d, J = 6.0 Hz, 1H), 8.31 (d, J = 8.8 Hz, 1H), 8.12 (d, J = 8.8 Hz, 1H), 7.65 (t, J = 8.0 Hz, 1H), 7.25 - 7.20 (m, 1H), 6.99 (d, J = 8.0 Hz, 1H), 4.46 - 4.40 (m, 1H), 2.44 - 2.36 (m, 2H), 2.19 - 2.09 (m, 3H), 1.62 - 1.48 (m, 4H). [0834] Step 3: 3-Nitro-5-((trans-4-(trifluoromethyl)cyclohexyl)oxy)quinolin e 1-oxide [0835] A solution of tert-butyl nitrite (0.31 mL, 2.57 mmol) in 1,2-dichloroethane (5 mL), then 5-((trans-4-(trifluoromethyl)cyclohexyl)oxy)quinoline 1-oxide (320 mg, 1.03 mmol) was added dropwise and the resulting mixture was stirred at 60°C for 24 hours. The mixture was concentrated under vacuum. The solution was quenched with water (30 mL) and then extracted with EtOAc (30 mL × 2). The organic layers were dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (0 - 30% ethyl acetate in petroleum ether) to afford the title compound (190 mg, 52%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 9.26 (d, J = 2.0 Hz, 1H), 8.92 (d, J = 1.2 Hz, 1H), 8.31 (d, J = 9.2 Hz, 1H), 7.86 (t, J = 8.4 Hz, 1H), 7.14 (d, J = 7.6 Hz, 1H), 4.57 - 4.45 (m, 1H), 2.45 - 2.39 (m, 2H), 2.22 - 2.12 (m, 3H), 1.75 - 1.65 (m, 2H), 1.63 (m, 2H). [0836] Step 4: 5-((trans-4-(Trifluoromethyl)cyclohexyl)oxy)quinolin-3-amine [0837] To a mixture of 3-nitro-5-((trans-4-(trifluoromethyl)cyclohexyl)oxy)quinolin e 1- oxide (160 mg, 0.45 mmol) in HOAc (4 mL) was added iron powder (150 mg, 2.69 mmol). The mixture was stirred at 60°C for 1 hour. The reaction mixture was cooled to room temperature and was filtered. The organic mixture was then concentrated under reduced pressure. The residue was purified by pre-TLC (30% ethyl acetate in petroleum ether) to afford the title compound (120 mg, 86%) as a yellow solid. ¹ H NMR (400 MHz,CD3OD): δ 8.40 (d, J = 2.4 Hz, 1H), 7.69 (d, J = 2.4 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.30 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 4.50 - 4.37 (m, 1H), 2.39 - 2.32 (m, 2H), 2.30 - 2.19 (m, 1H), 2.12 - 2.02 (m, 2H), 1.65 - 1.50 (m, 4H). [0838] Step 5: N-(5-((trans-4-(Trifluoromethyl)cyclohexyl)oxy)quinolin-3-yl )acrylamide [0839] To a mixture of 5-((trans-4-(trifluoromethyl)cyclohexyl)oxy)quinolin-3-amine (70 mg, 0.23 mmol) in DCM (2 mL) was added DIPEA (0.07 mL, 0.45 mmol) and the mixture was stirred at 0°C for 5 minutes. Acryloyl chloride (0.03 mL, 0.34 mmol) was added into the mixture at 0°C and reaction as stirred for 2 hours at 0°C. The mixture was diluted with water (30 mL) and the resultant mixture was extracted with DCM (30 mL × 3). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by pre-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 50/80) to afford the title compound (48 mg, 57%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 9.06 (s, 1H), 8.91 (s, 1H), 7.78 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H), 6.54 (d, J = 16.8 Hz, 1H), 6.35 (dd, J = 16.8, 10.0 Hz 1H), 5.86 (d, J = 10.0 Hz, 1H), 4.46 - 4.34 (m, 1H), 2.39 - 2.36 (m, 2H), 2.18 - 2.05 (m, 3H), 1.66 - 1.50 (m, 4H). LCMS (ESI): m/z 365.1 (M+H) ⁺ . EXAMPLE 39 [0840] Preparation of N-(5-((trans-4-(Trifluoromethyl)cyclohexyl)oxy)-1,6- naphthyridin-3- yl)acrylamide [0841] The overall reaction scheme was as follows: [0842] Step 1: 3-Bromo-1,6-naphthyridin-5(6H)-one [0843] To a mixture of ethyl 5-bromo-2-methylnicotinate (8.0 g, 32.77 mmol), 1,3,5- triazine (2.9 g, 36.05 mmol) in DMSO (80 mL) was stirred at room temperature for 30 minutes. Then t-BuOK (12.8 g, 39.33 mmol) was added into the mixture. The mixture was stirred at 80°C for 2 hours. The mixture was diluted with water (500 mL) and extracted with ethyl acetate (200 mL × 2), the organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 30% ethyl acetate in petroleum ether) to afford the title compound (1.2 g, 16%) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 9.00 (d, J = 2.0 Hz, 1H), 8.59 (d, J = 2.0 Hz, 1H), 7.50 (d, J = 7.6 Hz, 1H), 6.62 (d, J = 7.6 Hz, 1H). [0844] Step 2: 3-Bromo-5-chloro-1,6-naphthyridine [0845] POCl ₃ (2.49 mL, 26.66 mmol) was added into 3-bromo-1,6-naphthyridin-5(6H)- one (1.0 g, 4.44 mmol). The mixture was stirred at 100°C for 3 hours. The excess POCl3 was concentrated under reduced pressure. The residue was quenched with ice water (50 mL). Then the solution was adjusted to pH = 8 with 1N NaOH solution. The resulting solution was extracted with EtOAc (50 mL × 2) and the organic layers were dried over Na2SO4 and concentrated to afford the title compound (1.0 g, 92%) as a brown solid. ¹ H NMR (400MHz, DMSO-d ₆ ): δ 9.30 (d, J = 2.0 Hz, 1H), 8.87 (dd, J = 2.0, 0.8 Hz, 1H), 8.61 (d, J = 6.0 Hz, 1H), 8.00 (dd, J = 6.0, 0.8 Hz, 1H). [0846] Step 3: 3-Bromo-5-((trans-4- (trifluoromethyl)cyclohexyl)oxy)-1,6-naphthyridine [0847] To a mixture of 3-bromo-5-chloro-1,6-naphthyridine (400 mg, 1.64 mmol), trans- 4-(trifluoromethyl)cyclohexanol (414 mg, 2.46 mmol) in DMF (8 mL) was added NaH (60% in mineral oil, 131 mg, 3.29 mmol). The mixture was stirred at room temperature for 1 hour. The reaction was quenched with water (30 mL). The resulting solution was extracted with ethyl acetate (50 mL × 2) and the organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 10% ethyl acetate in petroleum ether) to afford the title compound (450 mg, 73%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 9.02 (d, J = 2.4 Hz, 1H), 8.66 (dd, J = 2.4, 0.8 Hz, 1H), 8.21 (d, J = 6.0 Hz, 1H), 7.44 (dd, J = 6.0, 0.8 Hz, 1H), 5.39 - 5.16 (m, 1H), 2.40 - 2.38 (m, 2H), 2.15 - 2.06 (m, 3H), 1.59 - 1.49 (m, 4H). [0848] Step 4: 5-((trans-4-(Trifluoromethyl)cyclohexyl)oxy)-1,6-naphthyridi n-3-amine [0849] To a solution of 3-bromo-5-((trans-4- (trifluoromethyl)cyclohexyl)oxy)-1,6- naphthyridine (200 mg, 0.53 mmol) in DMSO (5 mL) was added CuI (10 mg, 0.05 mmol) and K3PO4 (426 mg, 1.6 mmol), NH3 ^. H2O (0.04 mL, 1.07 mmol, 25%wt) and N ¹ ,N ² -bis(5-methyl- [1,1'-biphenyl]-2-yl)oxalamide (22 mg, 0.05 mmol). The reaction mixture was stirred at 120°C for 4 hours. The mixture was diluted with water (50 mL) and extracted with ethyl acetate (30 mL × 2) and the organic layers were dried over Na2SO4 and concentrated. The residue was purified by pre-TLC (30% ethyl acetate in petroleum ether) to afford the title compound (150 mg, 90%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.59 (d, J = 2.8 Hz, 1H), 7.95 (d, J = 6.0 Hz, 1H), 7.61 (d, J = 2.8 Hz, 1H), 7.34 (d, J = 6.0 Hz, 1H), 5.29 - 5.12 (m, 1H), 4.01 (s, 2H), 2.40 - 2.37 (m, 2H), 2.17 - 2.06 (m, 3H), 1.58 - 1.46 (m, 4H). [0850] Step 5: N-(5-((trans-4-(Trifluoromethyl)cyclohexyl)oxy)-1,6-naphthyr idin-3- yl)acrylamide [0851] To a mixture of 5-((trans-4-(trifluoromethyl)cyclohexyl)oxy)-1,6-naphthyridi n-3- amine (150 mg, 0.48 mmol), DIPEA (0.13 mL, 0.96 mmol) in DCM (4 mL) was added acryloyl chloride (0.04 mL, 0.48 mmol) at -78 ^o C. The mixture was stirred at -78 ^o C for 1 hour. The reaction was quenched with water (20 mL). The resulting solution was extracted with dichloromethane (30 mL × 2) and the organic layers were dried over Na2SO4 and concentrated. The residue was purified pre-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)- ACN; 55/85) to afford the title compound (89 mg, 50%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 10.76 (s, 1H), 9.16 (d, J = 2.4 Hz, 1H), 8.95 (d, J = 2.0 Hz, 1H), 8.12 (d, J = 6.0 Hz, 1H), 7.40 (dd, J = 6.0, 0.8 Hz, 1H), 6.48 (dd, J = 16.8, 10.0 Hz, 1H), 6.35 (dd, J = 16.8, 2.0 Hz, 1H), 5.86 (dd, J = 10.0, 2.0 Hz, 1H), 5.44 - 4.99 (m, 1H), 2.47 - 2.37 (m, 1H), 2.35 - 2.23 (m, 2H), 1.99 (m, 2H), 1.70 - 1.41 (m, 4H). LCMS (ESI): m/z 366.0 (M+H) ⁺ . EXAMPLE 40 [0852] Preparation of (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)benzo[d]oxazol-5- yl)acrylamide [0853] The overall reaction scheme was as follows: [0855] To a mixture of 4-bromo-2-methylphenol (23.0 g, 122.97 mmol) in glacial acetic acid (200 mL) at 0 ^o C was added nitric acid (7.09 mL, 159.87 mmol). The mixture was stirred at 0 ^o C for 30 minutes. Then the mixture was quenched with cold water and extracted with dichloromethane (200 mL × 2) and the organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (100% petroleum ether) to afford the title compound (14.0 g, 49%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 10.83 (s, 1H), 8.11 (s, 1H), 7.56 (s, 1H), 2.34 (s, 3H). [0856] Step 2: 2-Amino-4-bromo-6-methylphenol [0857] To a mixture of 4-bromo-2-methyl-6-nitrophenol (8.5 g, 36.63 mmol), NH4Cl (19.6 g, 366.33 mmol) in THF (170 mL) was added iron powder (20.0 g, 366.33 mmol). The mixture was stirred at 40 ^o C for 2 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated to afford the title compound (7.4 g, 100%) as a brown solid. The crude was used directly for the next step. ¹ H NMR (400 MHz, CDCl3): δ 6.77 (d, J = 2.4 Hz, 1H), 6.73 (d, J = 2.4 Hz, 1H), 4.68 (s, 1H), 3.66 (s, 2H), 2.20 (s, 3H). [0858] Step 3: 5-Bromo-7-methylbenzo[d]oxazole [0859] A mixture of 2-amino-4-bromo-6-methylphenol (7.4 g, 36.62 mmol), triethoxymethane (6.1 mL, 36.62 mmol) and Ga(OTf) ₃ (1.9 g, 3.66 mmol) was stirred at room temperature for 30 minutes, then the mixture was concentrated. The residue was purified by column chromatography on silica gel (0 - 30 % ethyl acetate in petroleum ether) to afford the title compound (4.8 g, 62%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.09 (s, 1H), 7.77 (s, 1H), 7.34 (s, 1H), 2.54 (s, 3H). [0860] Step 4: 5-Bromo-7-(bromomethyl)benzo[d]oxazole [0861] A mixture of AIBN (310 mg, 1.89 mmol), NBS (3.4 g, 18.86 mmol) and 5- bromo-7-methylbenzo[d]oxazole (4.0 g, 18.86 mmol) in CCl4 (40 mL) was stirred at 80 ^o C for 6 hours. The reaction was diluted with water (200 mL), extracted with EtOAc (200 mL × 3) and the combined organic layers were dried with Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 5% ethyl acetate in petroleum ether) to afford the title compound (1.5 g, 27%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.15 (s, 1H), 7.91 (d, J = 1.2 Hz, 1H), 7.56 (d, J = 1.2 Hz, 1H), 4.69 (s, 2H). [0862] Step 5: Diethyl ((5-bromobenzo[d]oxazol-7-yl)methyl)phosphonate [0863] A mixture of 5-bromo-7-(bromomethyl)benzo[d]oxazole (1.4 g, 4.81 mmol) and triethyl phosphite (0.83 mL, 4.81 mmol) was stirred at 120 ^o C for 3 hours. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (0 - 100% EtOAc in petroleum ether) to afford the title compound (0.87 g, 52%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.12 (s, 1H), 7.84 (s, 1H), 7.51 (s, 1H), 4.11 - 4.05 (m, 4H), 3.41 (d, J = 21.6 Hz, 2H), 1.26 (t, J = 7.2 Hz, 6H). [0864] Step 6: (E)-5-Bromo-7-(2-(4,4- difluorocyclohexyl)vinyl)benzo[d]oxazole [0865] To a solution of diethyl ((5-bromobenzo[d]oxazol-7-yl)methyl)phosphonate (800 mg, 2.3 mmol) in toluene (10 mL) at 0 ^o C was added sodium tert-pentoxide (329 mg, 2.99 mmol). After mixture was stirred at 0°C for 20 minutes, a solution of 4,4- difluorocyclohexanecarbaldehyde (Intermediate B, 3.0 g, 3.45 mmol) in THF (16 mL) was added dropwise and the mixture was stirred at 0 ^o C for 1.5 hours. Upon completion of the reaction, it was poured into saturated aqueous NH4Cl solution (50 mL) and extracted with EtOAc (50 mL × 2). The organic layers were washed with brine (50 mL). The organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography on silica gel (0 - 10% EtOAc in petroleum ether) to afford the title compound (300 mg, 38%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.13 (s, 1H), 7.79 (d, J = 2.0 Hz, 1H), 7.45 (d, J = 2.0 Hz, 1H), 6.67 (dd, J = 16.0, 6.8 Hz, 1H), 6.50 (d, J = 16.0 Hz, 1H), 2.40 - 2.29 (m, 1H), 2.23 - 2.12 (m, 2H), 1.98 - 1.90 (m, 2H), 1.89 - 1.74 (m, 2H), 1.70 - 1.61 (m, 2H). [0866] Step 7: (E)-7-(2-(4,4-Difluorocyclohexyl)vinyl)benzo[d]oxazol-5-amin e [0867] To a solution of (E)-5-bromo-7-(2-(4,4- difluorocyclohexyl)vinyl)benzo[d]oxazole (150 mg, 0.44 mmol) in DMSO (5 mL) added CuI (8 mg, 0.04 mmol) and K3PO4 (350 mg, 1.32 mmol), NH3 ^. H2O (0.03 mL, 0.88 mmol, 25%wt) and N ¹ ,N ² -bis(5-methyl-[1,1'-biphenyl]-2-yl)oxalamide (18 mg, 0.04 mmol). The solution was stirred at 120°C for 1 hour under a nitrogen atmosphere. The reaction mixture was diluted with water (30 ml) and extracted with EtOAc (30 mL × 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated. The residue was purified by pre-TLC (30% ethyl acetate in petroleum ether) to afford the title compound (10 mg, 8%) as a white solid. LCMS (ESI): m/z 279.1 (M+H) ⁺ . [0868] Step 8: (E)-N-(7-(2-(4,4-Difluorocyclohexyl)vinyl)benzo[d]oxazol-5- yl)acrylamide [0869] To a mixture of (E)-7-(2-(4,4-difluorocyclohexyl)vinyl)benzo[d]oxazol-5-amin e (20 mg, 0.07 mmol), TEA (0.02 mL, 0.14 mmol) in DCM (2 mL) was added acryloyl chloride (0.01 mL, 0.07 mmol) at -78 ^o C. The mixture was stirred at -78 ^o C for 1 hour. The reaction was quenched with water (20 mL). The resulting solution was extracted with DCM (20 mL × 2) and the organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by pre- HPLC (YMC Triart C18150*25mm*5um, water (10mM NH4HCO3)-ACN; 51/81) to afford the title compound (1 mg, 4%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.14 (s, 1H), 7.81 (s, 1H), 7.67 (s, 1H), 7.41 (s, 1H), 6.66 (dd, J = 16.0, 6.8 Hz, 1H), 6.56 (d, J = 16.0 Hz, 1H), 6.48 (d, J = 16.4 Hz, 1H), 6.28 (dd, J = 16.4, 10.4 Hz, 1H), 5.82 (d, J = 10.4 Hz, 1H), 2.33 (s, 1H), 2.24 - 2.10 (m, 2H), 1.93 (m, 2H), 1.88 - 1.73 (m, 2H), 1.70 - 1.62 (m, 2H). LCMS (ESI): m/z 333.0 (M+H) ⁺ . EXAMPLE 41 [0870] Preparation of N-(5-(4-isopropylphenyl)-6-methoxypyridin-3-yl)acrylamide [0871] The overall reaction scheme was as follows: [0872] Step 1: 3-(4-isopropylphenyl)-2-methoxy-5-nitropyridine [0873] A vial was charged with 3-bromo-2-methoxy-5-nitropyridine (284 mg, 1.2 mmol), (4-isopropylphenyl)boronic acid (260 mg, 1.6 mmol), potassium phosphate (95 mg, 2.4 mmol), SPhos pre-catalyst G3 (95 mg, 0.12 mmol), SPhos (90 mg, 0.17 mmol), toluene (10 mL), and water (1 mL). The reaction mixture was then vacuum purged / back-filled with N2 (3X). The vial was capped, and the reaction mixture was stirred at 95 °C for 22 hours. The cooled reaction mixture was diluted with ⁱ PrOAc and filtered through a pad of Celite®. The pad was rinsed with additional ⁱ PrOAc. The filtrate was washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography (SiO2: ⁱ PrOAc / heptane) to obtain 3-(4-isopropylphenyl)-2-methoxy-5-nitropyridine (312 mg, 91.3% yield). ¹ H NMR (400 MHz, CDCl3) δ 9.04 (d, J = 2.7 Hz, 1H), 8.40 (d, J = 2.7 Hz, 1H), 7.54 – 7.48 (m, 2H), 7.36 – 7.32 (m, 2H), 4.09 (s, 3H), 3.04 – 2.91 (m, 1H), 1.30 (d, J = 6.9 Hz, 6H); LCMS (ESI): m/z 273 (M+H) ⁺ . [0874] Step 2: 5-(4-isopropylphenyl)-6-methoxypyridin-3-amine [0875] To a mixture of 3-(4-isopropylphenyl)-2-methoxy-5-nitro-pyridine (298 mg, 1.09 mmol) dissolved in EtOH (22 mL) was added ammonium chloride (585 mg, 10.9 mmol) in water (4.4 mL), followed by iron powder (306 mg, 5.47 mmol). The reaction mixture was stirred at reflux for 1 hour. The reaction mixture was cooled to RT and filtered through a pad of Celite®. The pad of rinsed well with DCM and EtOH. The filtrate was basified with sat. aq. NaHCO3 solution until pH ~7 and then extracted with ⁱ PrOAc (3x). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude products were purified by column chromatography (SiO2: ⁱ PrOAc / heptane) to obtain 196 mg (74% yield) of 5-(4-isopropylphenyl)-6-methoxypyridin-3-amine. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.64 (d, J = 2.8 Hz, 1H), 7.48 (d, J = 7.9 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 7.08 (d, J = 2.8 Hz, 1H), 3.90 (s, 3H), 3.40 (s, 2H), 3.01 – 2.87 (m, 1H), 1.28 (d, J = 6.9 Hz, 6H); LCMS (ESI): m/z 243 (M+H) ⁺ . [0876] Step 3: N-(5-(4-isopropylphenyl)-6-methoxypyridin-3-yl)acrylamide [0877] To a mixture of 5-(4-isopropylphenyl)-6-methoxypyridin-3-amine (83 mg, 0.34 mmol), acrylic acid (125 mg, 1.72 mmol, 0.12 mL), and HATU (266 mg, 0.69 mmol,) in anhydrous DMF (3.4 mL) was added DIPEA (444 mg, 3.43 mmol, 0.60 mL), and the reaction mixture was stirred at RT for 4 days. The reaction mixture was diluted with ⁱ PrOAc, and the organic layer was washed with water, 50% brine (2X), brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography (SiO ₂ : ⁱ PrOAc / heptane) followed by reverse-phase preparative HPLC to afford 31 mg (30.3% yield) of the title compound as a white solid. ¹ H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.41 (d, J = 2.5 Hz, 1H), 8.03 (d, J = 2.6 Hz, 1H), 7.51 – 7.42 (m, 2H), 7.36 – 7.28 (m, 2H), 6.42 (dd, J = 16.9, 10.1 Hz, 1H), 6.26 (dd, J = 16.9, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 2.1 Hz, 1H), 3.86 (s, 3H), 2.99 – 2.87 (m, 1H), 1.24 (d, J = 6.9 Hz, 6H); LCMS (ESI): m/z 297 (M+H) ⁺ . EXAMPLE 42 [0878] Preparation of N-(6-methoxy-5-((E)-2-((3S,6S)-6-(trifluoromethyl)tetrahydro -2H- pyran-3-yl)vinyl)pyridin-3-yl)acrylamide (Compound 43) and N-(6-methoxy-5-((E)-2-((3R,6R)- 6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)vinyl)pyridin-3- yl)acrylamide (Compound 44) [0879] The overall reaction scheme was as follows: [0880] Step 1: (E)-5-bromo-2-methoxy-3-(2-(6-(trifluoromethyl)tetrahydro-2H -pyran-3- yl)vinyl)pyridine [0881] To a mixture of 5-bromo-3-(diethoxyphosphorylmethyl)-2-methoxy-pyridine (500 mg, 1.48 mmol), trans-6-(trifluoromethyl)tetrahydro-2H-pyran-3-carbaldehyde (539 mg, 2.97 mmol) in anhydrous THF (30 mL) was added sodium tert-butoxide (686 mg, 5.92 mmol, 3743.9 mg), and the reaction mixture was stirred at RT under N2 for 3 hours. Volatile solvent was removed, and the crude residue was diluted with ⁱ PrOAc. The organic layer was washed with water and brine, dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The crude product was purified by column chromatography (SiO2: ⁱ PrOAc/heptane) to give (E)-5-bromo-2- methoxy-3-(2-(6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)vi nyl)pyridine (253 mg, 46.7%) as an oil. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.06 (d, J = 2.4 Hz, 1H), 7.69 (d, J = 2.5 Hz, 1H), 6.54 (dd, J = 16.3, 1.3 Hz, 1H), 6.04 (dd, J = 16.2, 7.4 Hz, 1H), 4.15 – 4.07 (m, 1H), 3.95 (s, 3H), 3.75 – 3.65 (m, 1H), 3.29 (t, J = 11.2 Hz, 1H), 2.60 – 2.48 (m, 1H), 2.10 (m, 1H), 1.90 (m, 1H), 1.69 (m, 1H), 1.50 (m, 1H); LCMS (ESI): m/z 366 (M+H) ⁺ . [0882] Step 2: (E)-6-methoxy-5-(2-(6-(trifluoromethyl)tetrahydro-2H-pyran-3 - yl)vinyl)pyridin-3-amine [0883] In a 20-mL vial was placed (E)-5-bromo-2-methoxy-3-(2-(6- (trifluoromethyl)tetrahydro-2H-pyran-3-yl)vinyl)pyridine (113 mg, 0.31 mmol), diphenylmethanimine (84 mg, 0.46 mmol), sodium tert-butoxide (59 mg, 0.62 mmol), bis(2- diphenylphosphinophenyl)ether (17 mg, 0.03 mmol), and tris(dibenzylidenteactone)dipalladium(0) (14 mg, 0.015 mmol). Degassed toluene (2 mL) was added. The vial was vacuum purged / back-filled with N ₂ (3x) and capped. The reaction mixture was stirred at 120 °C for 18 hours. The reaction mixture was diluted with ⁱ PrOAc and water, and then filtered through a pad of Celite®. The biphasic layers were separated. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified by column chromatography (SiO ₂ : ⁱ PrOAc / heptane) to obtain intermediate (E)-N-(6-methoxy-5-(2-(6-(trifluoromethyl)tetrahydro-2H-pyra n-3-yl)vinyl)pyridin- 3-yl)-1,1-diphenylmethanimine. This was then dissolved in THF (5.6 mL) and 1N HCl (1.4 mL, 1.4 mmol) was added. The reaction mixture was stirred at RT for 2 hours. Volatile solvent was removed under reduced pressure, and the crude residue was diluted with DCM. The reaction mixture was then basified with sat. aq. NaHCO3 solution until pH ~ 8, then extracted with DCM (3x). The combined organic layers were washed with water and brine, dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude was purified by column chromatography (SiO2: ⁱ PrOAc / heptane) to give (E)-6-methoxy-5-(2-(6- (trifluoromethyl)tetrahydro-2H-pyran-3-yl)vinyl)pyridin-3-am ine (85.3 mg, 78.4% yield) as an oil. LCMS (ESI): m/z 303 (M+H) ⁺ . [0884] Step 3: N-(6-methoxy-5-((E)-2-((3S,6S)-6-(trifluoromethyl)tetrahydro -2H-pyran- 3-yl)vinyl)pyridin-3-yl)acrylamide and N-(6-methoxy-5-((E)-2-((3R,6R)-6- (trifluoromethyl)tetrahydro-2H-pyran-3-yl)vinyl)pyridin-3-yl )acrylamide [0885] To a mixture of (E)-6-methoxy-5-(2-(6-(trifluoromethyl)tetrahydro-2H-pyran-3 - yl)vinyl)pyridin-3-amine (73 mg, 0.24 mmol), acrylic acid (88 mg, 1.21 mmol, 0.084 mL), and HATU (188 mg, 0.48 mmol,) in anhydrous DMF (2.4 mL) was added DIPEA (313 mg, 2.42 mmol, 0.42 mL), and the reaction mixture was stirred at RT for 2 days. The reaction mixture was diluted with ⁱ PrOAc, and the organic layer was washed with water, 50% brine (2X), brine, dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The crude product was purified by column chromatography (SiO2: ⁱ PrOAc / heptane) to give racemic (E)-N-(6-methoxy-5-(2-(6- (trifluoromethyl)tetrahydro-2H-pyran-3-yl)vinyl)pyridin-3-yl )acrylamide. This was subjected to chiral SFC (Chiralpak AD column, 15% MeOH w/ 0.1% NH ₄ OH) to give 22.7 mg (26.3% yield) of N-(6-methoxy-5-((E)-2-(6-(trifluoromethyl)tetrahydro-2H-pyra n-3-yl)vinyl)pyridin-3- yl)acrylamide, Enantiomer A (with a retention time of 0.796 min) and 11 mg (12.9% yield) of N- (6-methoxy-5-((E)-2-(6-(trifluoromethyl)tetrahydro-2H-pyran- 3-yl)vinyl)pyridin-3- yl)acrylamide, Enantiomer B (with a retention time of 0.964 min). [0886] Enantiomer A: ¹ H NMR (400 MHz, DMSO-d6): δ 10.17 (s, 1H), 8.27 (d, J = 2.5 Hz, 1H), 8.12 (d, J = 2.6 Hz, 1H), 6.57 (dd, J = 16.3, 1.3 Hz, 1H), 6.40 (dd, J = 17.0, 10.0 Hz, 1H), 6.25 (dd, J = 17.0, 2.1 Hz, 1H), 6.12 (dd, J = 16.2, 7.3 Hz, 1H), 5.77 (dd, J = 10.0, 2.1 Hz, 1H), 4.06 – 3.95 (m, 2H), 3.88 (s, 3H), 3.33 (t, J = 11.1 Hz, 2H), 2.04 – 1.94 (m, 1H), 1.89 – 1.77 (m, 1H), 1.63 – 1.47 (m, 2H); LCMS (ESI): m/z 357.2 (M+H) ⁺ . [0887] Enantiomer B: ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.17 (s, 1H), 8.27 (d, J = 2.5 Hz, 1H), 8.12 (d, J = 2.5 Hz, 1H), 6.57 (dd, J = 16.3, 1.2 Hz, 1H), 6.40 (dd, J = 16.9, 10.0 Hz, 1H), 6.25 (dd, J = 17.0, 2.0 Hz, 1H), 6.12 (dd, J = 16.2, 7.3 Hz, 1H), 5.77 (dd, J = 10.0, 2.1 Hz, 1H), 4.06 – 3.95 (m, 2H), 3.88 (s, 3H), 3.33 (t, J = 11.1 Hz, 2H), 2.04 – 1.94 (m, 1H), 1.89 – 1.77 (m, 1H), 1.63 – 1.47 (m, 2H); LCMS (ESI): m/z 357.2 (M+H) ⁺ . EXAMPLE 43 [0888] Preparation of (R)-N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5 - yl)-2-methyloxirane-2-carboxamide and (S)-N-(4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)-2-methyloxirane-2-carboxamide [0889] The overall reaction scheme was as follows: [0890] Step 1: Preparation of N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran- 5-yl)methacrylamide [0891] A solution of 5-amino-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-4- carbonitrile (500 mg, 1.80 mmol), methacrylic acid (464 mg, 5.39 mmol), TEA (0.55 g, 5.39 mmol), DMAP (20 mg, 0.18 mmol) and T ₃ P (1.72 g, 5.40 mmol, 50% in ethyl acetate) in ethyl acetate (5 mL) was stirred at room temperature for 16 hours. At which point, the reaction was concentrated. The residue was purified by prep-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 55/85) to afford the title compound (340 mg, 55%) as a yellowish solid. ¹ H NMR (400 MHz, CDCl3): δ 8.29 (s, 1H), 7.83 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 5.94 (s, 1H), 5.56 (d, J = 1.6 Hz, 1H), 4.73 (t, J = 8.8 Hz, 2H), 3.45 (t, J = 8.8 Hz, 2H), 2.98 - 2.92 (m, 1H), 2.12 (s, 3H), 1.28 (d, J = 6.8 Hz, 6H). LCMS (ESI): m/z 347.1 (M+H) ⁺ . [0892] Step 2: Preparation of N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran- 5-yl)-2-methyloxirane-2-carboxamide [0893] To a mixture of N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5- yl)methacrylamide (210 mg, 0.61 mmol) in DCM (14 mL) was added H2O2 (0.24 mL, 2.42 mmol) and TFFA (0.43mL, 3.03mmol). The mixture was stirred at room temperature for 18 hours. The reaction was washed with sat. aq. Na2SO3 solution (5 mL) and then sat. aq. NaHCO3 solution (3 mL). The reaction was diluted with water (20 mL) and extracted with dichloromethane (40 mL × 2). The combined organics were washed with brine (20 mL × 2), dried Na ₂ SO ₄ , filtered and concentrated. The residue was purified by flash chromatography on silica gel (0 - 10% ethyl acetate in petroleum ether) to afford the title compound (62 mg, 28%) as a white solid. LCMS (ESI): m/z 385.0 (M+Na) ⁺ . [0894] Step 3: Preparation of (R)-N-(4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)-2-methyloxirane-2-carboxamide and (S)-N-(4-cyano-7-(4- isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)-2-methyloxirane -2-carboxamide [0895] N-(4-Cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl) -2- methyloxirane-2-carboxamide (60 mg, 0.17 mmol) was separated by chiral SFC (DAICEL CHIRALPAK AD(250mm*30mm,10um); Neu-IPA, 35%) to afford the title compounds (R)-N- (4-Cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)-2 -methyloxirane-2-carboxamide and (S)-N-(4-Cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5 -yl)-2-methyloxirane-2- carboxamide as a white solid. [0896] First peak on SFC = Enantiomer A: yield of 2.74 mg, 4%; ¹ H NMR (400 MHz, DMSO-d6): δ 9.68 (s, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.34 (s, 1H), 4.71 (t, J = 8.8 Hz, 2H), 3.42 (t, J = 8.8 Hz, 2H), 3.03 - 3.00 (m, 2H), 2.93 - 2.89 (m, 1H), 1.54 (s, 3H), 1.23 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 385.0 (M+Na) ⁺ . [0897] Second peak on SFC = Enantiomer B: yield of 8.51 mg, 14%; ¹ H NMR (400 MHz, DMSO-d6): δ 9.67 (s, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.33 (s, 1H), 4.70 (t, J = 8.8 Hz, 2H), 3.41 (t, J = 8.8 Hz, 2H), 3.06 - 3.01 (m, 2H), 2.96 - 2.89 (m, 1H), 1.53 (s, 3H), 1.22 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 363.0 (M+H) ⁺ . EXAMPLE 44 [0898] Preparation of (S)-N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5 - yl)oxirane-2-carboxamide [0899] The overall reaction scheme was as follows: [0900] Step 1: Preparation of (2S)-oxirane-2-carboxylic acid, sodium salt [0901] To a mixture of (S)-methyl oxirane-2-carboxylate (500 mg, 4.90 mmol) in MeOH (10 mL) was added NaOH (205 mg, 5.1 mmol) at 0°C, the mixture was stirred at room temperature for 16 hours. The organic layer was concentrated to afford the title compound (460 mg, 85%) as a white solid and used without any further purification. [0902] Step 2: Preparation of (S)-N-(4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)oxirane-2-carboxamide [0903] A solution of DMAP (11 mg, 0.09 mmol), 5-amino-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-4-carbonitrile (250 mg, 0.90 mmol), (2S)-oxirane-2-carboxylic acid sodium salt (148 mg, 1.35 mmol), Et3N (0.38 mL, 2.69 mmol) and T3P (1.7 g, 2.7 mmol, 50% in ethyl acetate) in EtOAc (5 mL) was stirred at 80°C for 3 hours. The reaction solution was purified by column chromatography on silica gel (0 - 25% ethyl acetate in petroleum ether) to afford the title compound (32 mg, 10%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.09 (s, 1H), 8.04 (s, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 4.73 (t, J = 8.8 Hz, 2H), 3.65 -3.62 (m, 1H), 3.44 (t, J = 8.8 Hz, 2H), 3.18 - 3.15 (m, 1H), 3.05 - 3.02 (m, 1H), 2.96 - 2.88 (m, 1H), 1.28 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 349.0 (M+H) ⁺ . EXAMPLE 45 [0904] Preparation of (R)-N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5 - yl)oxirane-2-carboxamide [0905] The overall reaction scheme was as follows: [0906] Step 1: (2R)-oxirane-2-carboxylic acid, sodium salt [0907] To a mixture of methyl (R)-methyl oxirane-2-carboxylate (1.0 g, 9.8 mmol) in MeOH (20 mL) was added NaOH (411 mg, 10.29 mmol), the mixture was stirred at room temperature for 16 hours. The organic layer was concentrated under vacuum. The organic layer was concentrated to afford the title compound (900 mg, 84%) as white solid and used without any further purification. [0908] Step 2: Preparation of (R)-N-(4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)oxirane-2-carboxamide [0909] A solution of DMAP (9 mg, 0.07 mmol), 5-amino-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-4-carbonitrile (200 mg, 0.72 mmol), (2R)-oxirane-2-carboxylic acid, sodium salt (119 mg, 1.08 mmol), Et3N (0.3 mL, 2.16 mmol) and T3P (1.4 g, 2.16 mmol, 50% in ethyl acetate) in EtOAc (5 mL) was stirred at 80°C for 3 hours. The reaction solution was purified by column chromatography on silica gel (0 - 25% ethyl acetate in petroleum ether) to afford the title compound (33 mg, 13%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 8.09 (s, 1H), 8.04 (s, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 4.73 (t, J = 8.8 Hz, 2H), 3.65 -3.62 (m, 1H), 3.44 (t, J = 8.8 Hz, 2H), 3.18 - 3.15 (m, 1H), 3.05 - 3.02 (m, 1H), 2.96 - 2.88 (m, 1H), 1.28 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 349.0 (M+H) ⁺ . [0910] EXAMPLE 46 [0911] Preparation of 1-cyano-3-(4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)-1-methylurea [0912] The overall reaction scheme was as follows: [0913] Step 1: Preparation of N-methylcyanamide [0914] To a solution of cyanic bromide (8.88 g, 83.84 mmol) and Na ₂ CO ₃ (19.62 g, 185.13 mmol) in THF (100 mL) was added methanamine hydrochloride (5.0 g, 74.05 mmol) at - 78°C. The reaction solution was stirred for 3 hours at -20°C. The reaction solution was filtrated and the solution was used for next step directly. [0915] Step 2: Preparation of 5-isocyanato-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-4-carbonitrile [0916] To a mixture of 5-amino-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-4- carbonitrile (200 mg, 0.72 mmol) and TEA (0.3 mL, 2.16 mmol) in dichloromethane (10 mL) was added bis(trichloromethyl) carbonate (450 mg, 1.52 mmol), the mixture was stirred at 0°C for 3 hours. The reaction solution was concentrated to afford the crude title compound (200 mg) as a yellow solid which was used for next step directly. [0917] Step 3: Preparation of 1-cyano-3-(4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)-1-methylurea [0918] To a mixture of 5-isocyanato-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-4- carbonitrile (200 mg, 0.66 mmol), triethylamine (199 mg, 1.97 mmol) in dichloromethane (10 mL) was added 0.7 M N-methylcyanamide in THF (10 mL, 7 mmol), the mixture was stirred at 0°C for 3 hours. The reaction solution was washed with brine (10 mL) and concentrated. The residue was purified by prep-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)- ACN; 60/90) to afford the title compound (43.17 mg, 18%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 9.89 (s, 1H), 7.64 (d, J = 7.6 Hz, 2H), 7.41 (s, 1H), 7.35 (d, J = 7.6 Hz, 2H), 4.72 (t, J = 8.4 Hz, 2H), 3.44 (d, J = 8.4 Hz, 2H), 3.29 (s, 3H), 2.96 - 2.86 (m, 1H), 1.22 (d, J = 6.8 Hz, 3H); LCMS (ESI): m/z 361.0 (M+H) ⁺ . EXAMPLE 47 [0919] Preparation of 3-cyano-1-[4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl]-1-methyl-urea [0920] The overall reaction scheme was as follows: [0921] Step 1: Preparation of 1-cyano-3-[4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl]urea [0922] To a solution of sodium hydroxide (107 mg, 2.66 mmol) in water (2 mL) was added cyanamide (298 mg, 7.1 mmol). Then 5-isocyanato-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-4-carbonitrile (540 mg, 1.77 mmol) in dichloromethane (5 mL) was added into it dropwise over 10 minutes at room temperature. The resulting solution was stirred at room temperature for 30 minutes. The mixture was quenched with 2 M HCl (5 mL). Extracted with EtOAc (50 mL × 2). Combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated to afford the title compound (500 mg, 81%) as a yellow solid which was used for next step directly without further purification. LCMS (ESI): m/z 347.1 (M+H) ⁺ . [0923] Step 2: Preparation of 3-cyano-1-[4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl]-1-methyl-urea [0924] To a solution of 1-cyano-3-[4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl]urea (200 mg, 0.66 mmol) and sodium hydroxide (27 mg, 0.66 mmol) in water (2 mL) was added dimethyl sulfate (0.56 mL, 0.66 mmol) in dichloromethane (3mL). The resulting solution was stirred at 0°C for 2 hours. The reaction mixture was purified by prep- HPLC (Welch Xtimate C18150*25mm*5um, water (0.2%FA)-CAN,56%-86%) to afford the title compound (21 mg, 10%) as a yellow solid which was confirmed by 2D-NMR (HMBC). ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 11.76 (s, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.08 (s, 1H), 4.62 (t, J = 8.8 Hz, 2H), 3.79 (s, 3H), 3.61 (t, J = 8.8 Hz, 2H), 2.96 - 2.93 (m, 1H), 1.24 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 361.2 (M+H) ⁺ . EXAMPLE 48 [0925] Preparation of (S)-N-(4-cyano-7-(4-(1,1-difluoroethyl)phenyl)-2,3- dihydrobenzofuran-5-yl)oxirane-2-carboxamide [0926] The overall reaction scheme was as follows: [0927] Step 1: 5-amino-7-(4-(1,1-difluoroethyl)phenyl)-2,3-dihydrobenzofura n-4- carbonitrile [0928] To a solution of 5-amino-7-chloro-2,3-dihydrobenzofuran-4-carbonitrile (500 mg, 2.6 mmol) in 1,4-dioxane (5 mL) was added Potassium Acetate (504 mg, 5.2 mmol), Xphos Pd G2 (202 mg, 0.26 mmol), Xphos (122 mg, 0.26 mmol) and 2-(4-(1,1-difluoroethyl)phenyl)- 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1033 mg, 3.9 mmol). The resulting mixture was stirred at 80°C under N2 atmosphere for 4 hours. The mixture was diluted with water (20 mL) and extracted with EtOAc (10 mL × 3). The combined organic layers were dried over Na ₂ SO ₄ and concentrated under vacuum. The residue was purified by chromatography on silica (0-10% EtOAc in petroleum ether) to afford the title compound (300 mg, 39%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.71 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 6.69 (s, 1H), 4.66 (t, J = 8.8 Hz, 2H), 4.12 (s, 2H), 3.38 (t, J = 8.8 Hz, 2H), 1.95 (t, J = 18.4 Hz, 3H); LCMS (ESI): m/z 301.1 (M+H) ⁺ . [0929] Step 2: Preparation of (S)-N-(4-cyano-7-(4-(1,1-difluoroethyl)phenyl)-2,3- dihydrobenzofuran-5-yl)oxirane-2-carboxamide [0930] A solution of DMAP (4 mg, 0.03 mmol), 5-amino-7-(4-(1,1- difluoroethyl)phenyl)-2,3-dihydrobenzofuran-4-carbonitrile (100 mg, 0.33 mmol), sodium (S)- oxirane-2-carboxylate (73 mg, 0.66 mmol), TEA (0.14 mL, 1.00 mmol) and T ₃ P (636 mg, 1.00 mmol, 50% in ethyl acetate) in EtOAc (1 mL) was stirred at room temperature for 1 hour. The reaction solution was diluted with EtOAc (10 mL) and washed with water (10 mL × 3). The combined organics were dried over Na ₂ SO ₄ and concentrated. The residue was purified by prep- TLC ( 30% ethyl acetate in petroleum ether) to afford the title (36.47 mg, 30%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 10.19 (s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.47 (s, 1H), 4.74 (t, J = 8.8 Hz, 2H), 3.70 - 3.58 (m, 1H), 3.43 (t, J = 8.8 Hz, 2H), 3.12 - 3.03 (m, 1H), 2.97 - 2.87 (m, 1H), 1.99 (t, J = 18.8 Hz, 3H). LCMS (ESI): m/z 371.0 (M+H) ⁺ . EXAMPLE 49 [0931] Preparation of (R)-N-(4-cyano-7-(4-(1,1-difluoroethyl)phenyl)-2,3- dihydrobenzofuran-5-yl)oxirane-2-carboxamide [0932] The overall reaction scheme was as follows: [0933] A solution of DMAP (4 mg, 0.03 mmol), 5-amino-7-(4-(1,1- difluoroethyl)phenyl)-2,3-dihydrobenzofuran-4-carbonitrile (100 mg, 0.33 mmol), sodium (R)- oxirane-2-carboxylate (73 mg, 0.66 mmol), TEA (0.14 mL, 1.0 mmol) and T3P (636 mg, 1.0 mmol, 50% in ethyl acetate) in EtOAc (1 mL) was stirred at room temperature for 1 hour. The reaction solution was diluted with EtOAc (5 mL) and washed with water (10 mL × 3), the organic was dried over Na2SO4 and concentrated. The residue was purified by prep-TLC ( 30% ethyl acetate in petroleum ether) to afford the title compound (36.56 mg, 30%) as a white solid. ¹ H NMR (400MHz, DMSO-d ₆ ): δ 10.19 (s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.48 (s, 1H), 4.74 (t, J = 8.8 Hz, 2H), 3.70 - 3.56 (m, 1H), 3.45 (t, J = 8.8 Hz, 2H), 3.10 - 3.02 (m, 1H), 2.99 - 2.89 (m, 1H), 1.99 (t, J = 18.8 Hz, 3H); LCMS (ESI): m/z 371.0 (M+H) ⁺ . [0934] EXAMPLE 50 [0935] Preparation of (S)-N-(4-cyano-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-5-yl)oxirane-2-carboxamide [0936] The overall reaction scheme was as follows: [0937] A solution of 5-amino-7-(4-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofuran -4- carbonitrile (80 mg, 0.25 mmol), (2S)-oxirane-2-carboxylic acid, sodium salt (83 mg, 0.75 mmol), DMAP (4 mg, 0.02 mmol), TEA (0.1 mL, 0.75 mmol) and T3P(477 mg, 0.75 mmol, 50% in ethyl acetate) in ethyl acetate (3 mL) was stirred at room temperature for 3 hours. The reaction solution was purified prep-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 55/85) to afford the title compound (8.84 mg, 9%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 10.20 (s, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 7.47 (s, 1H), 4.73 (t, J = 8.8 Hz, 2H), 3.65 - 3.64 (m, 1H), 3.45 (t, J = 8.8 Hz, 2H), 3.10 - 3.02 (m, 1H), 2.94 - 2.92 (m, 1H); LCMS (ESI): m/z 391.0 (M+H) ⁺ . EXAMPLE 51 [0938] Preparation of (R)-N-(4-Cyano-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-5-yl)oxirane-2-carboxamide [0939] The title compound (33.6 mg, 53%) was furnished as a white solid. It was prepared from 5-amino-7-(4-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofuran -4-carbonitrile (50 mg, 0.16 mmol), (2R)-oxirane-2-carboxylic acid, sodium salt (26 mg, 0.23 mmol) following the procedure outlined for Example 50. The residue was purified by prep-HPLC (Boston Green ODS 150*30mm*5um; water (0.2%FA)-ACN; 55/85). ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.20 (s, 1H), 7.83 (dd, J = 8.8, 2.0 Hz, 2H), 7.48 (d, J = 8.8 Hz, 3H), 4.74 (t, J = 8.8 Hz, 2H), 3.47- 3.43 (m, 1H), 3.45 (t, J = 8.8 Hz, 2H), 3.10 - 3.06 (m, 1H), 2.95 - 2.92 (m, 1H); LCMS (ESI): m/z 391.0 (M+H) ⁺ . EXAMPLE 52 [0940] Preparation of (R)-2-(3-Amino-3-oxopropyl)-N-(4-cyano-7-(4-isopropylphenyl) - 2,3-dihydrobenzofuran-5-yl)oxirane-2-carboxamide and (S)-2-(3-amino-3-oxopropyl)-N-(4- cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)oxira ne-2-carboxamide [0941] The general reaction scheme was as follows: [0942] Step 1: Preparation of 1,1-Dibenzyl 3-tert-butyl propane-1,1,3-tricarboxylate [0943] To a solution of dibenzyl malonate (22.18 g, 78.02 mmol) in THF (100 mL) was added NaH (312 mg, 7.8 mmol) slowly at 0°C and the mixture was stirred at 0°C for 30 min. Then a solution of tert-butyl acrylate (10.0 g, 78.02 mmol) in THF (50 mL) was added slowly at 0°C. After addition, the reaction mixture was stirred for 5 hours at room temperature. The reaction was quenched with sat. aq. NH ₄ Cl (300 mL) and extracted with EtOAc (500 mL × 2). The combined organic layers were washed with brine (200 mL × 2) and the organic layer was dried over Na2SO4 and concentrated. The residue was purified by flash chromatography on silica gel (0 - 10% ethyl acetate in petroleum ether) to afford the title compound (30.0 g, 93%) as a colorless oil. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.35 - 7.29 (m, 10H), 5.16 (s, 4H), 3.56 (t, J = 7.2 Hz, 1H), 2.33 - 2.26 (m, 2H), 2.25 - 2.19 (m, 2H), 1.43 (s, 9H). [0944] Step 2: Preparation of 2-(3-(tert-Butoxy)-3-oxopropyl)malonic acid [0945] A solution of 1,1-dibenzyl 3-tert-butyl propane-1,1,3-tricarboxylate and 10% Pd/C (0.77 g, 7.27 mmol) in THF (300 mL) was stirred for 16 hours under an atmosphere of H2 (15 psi). The mixture solution was filtered and concentrated to afford the title compound (16.0 g, 95%) as a colorless oil. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 12.9 (s, 2H), 3.27 - 3.23 (m, 1H), 2.25 - 2.21 (m, 2H), 1.93 - 1.87 (m, 2H), 1.39 (s, 9H). [0946] Step 3: Preparation of 5-(tert-Butoxy)-2-methylene-5-oxopentanoic acid [0947] A solution of 2-(3-(tert-butoxy)-3-oxopropyl)malonic acid (16.0 g, 68.9 mmol), formaldehyde (80.0 mL, 344.49 mmol, 37 wt % in H2O) and diethylamine (10.0 g, 137.79 mmol) was stirred at 100°C for 3 hours. The reaction mixture was adjusted to pH 1 with aq.1M HCl solution. Then the mixture was extracted with EtOAC (300 mL × 3). The organic layer was washed with water (200 mL × 3), dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (0 - 50% ethyl acetate in petroleum ether) to afford the title compound (9.0 g, 65%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 6.34 (s, 1H), 5.73 (s, 1H), 2.61 (t, J = 7.6 Hz, 2H), 2.46 (t, J = 7.6 Hz, 2H), 1.45 (s, 9H). [0948] Step 4: Preparation of tert-Butyl 4-((4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)carbamoyl)pent-4-enoate [0949] A solution of 5-amino-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-4- carbonitrile (1.0 g, 3.59 mmol), 5-(tert-butoxy)-2-methylene-5-oxopentanoic acid (1.08 g, 5.39 mmol), DMAP (44 mg, 0.36 mmol), TEA (2.5 mL, 17.96 mmol) and T ₃ P (3.42 g, 5.39 mmol, 50% in ethyl acetate) in ethyl acetate (10 mL) was stirred at 50°C for 3 hours. The mixture was quenched with water (100 mL) and extracted with EtOAc (200 mL × 3). The organic layer was washed with water (100 mL × 3), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by flash chromatography on silica gel (0 - 25% ethyl acetate in petroleum ether) to afford the title compound (1.0 g, 60%) as a colorless liquid. ¹ H NMR (400 MHz, CDCl3): δ 8.17 (s, 1H), 8.04 (s, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 5.90 (s, 1H), 5.55 (s, 1H), 4.72 (t, J = 8.8 Hz, 2H), 3.45 (t, J = 8.8 Hz, 2H), 3.00 - 2.90 (m, 1H), 2.77 - 2.68 (m, 2H), 2.56 - 2.48 (m, 2H), 1.46 (s, 9H), 1.28 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 405.1 (M-56+H) ⁺ . [0950] Step 5: Preparation of 4-((4-Cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)carbamoyl)pent-4-enoic acid [0951] A mixture of tert-butyl 4-((4-cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)carbamoyl)pent-4-enoate(1.0 g, 2.17 mmol) and 5% TFA in HFIP (Hexafluoroisopropanol, 20 mL) was stirred at room temperature for 16 hours. The reaction mixture was concentrated. The residue was purified by flash chromatography on silica gel (0 - 50% ethyl acetate in petroleum ether) to afford the title compound (700 mg, 79%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.13 (s, 1H), 7.97 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 5.89 (s, 1H), 5.59 (s, 1H), 4.72 (t, J = 8.8 Hz, 2H), 3.44 (t, J = 8.8 Hz, 2H), 3.00 - 2.90 (m, 1H), 2.80 - 2.70 (m, 2H), 2.70 - 2.65 (m, 2H), 1.28 (d, J = 6.8 Hz, 6H). [0952] Step 6: Preparation of N ¹ -(4-Cyano-7-(4-isopropylphenyl)-2,3- dihydrobenzofuran-5-yl)-2-methylenepentanediamide [0953] To a mixture of 4-((4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran-5- yl)carbamoyl)pent-4-enoic acid (500 mg, 1.24 mmol), NH ₄ Cl (661 mg, 12.36 mmol) and DIPEA (2.39 g, 18.54 mmol) in DMF (5 mL) was added HATU (705 mg, 1.85 mmol). Then the mixture was stirred at room temperature for 16 hours. The mixture was purified directly by prep-HPLC (Boston Uni C1840*150*5um, water(0.225%FA)-ACN, 50-80%) to afford the title compound (220 mg, 44%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.22 (s, 1H), 7.93 (s, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 5.97 - 5.87 (m, 3H), 5.60 (s, 1H), 4.72 (t, J = 8.8 Hz, 2H), 3.44 (t, J = 8.8 Hz, 2H), 3.01 - 2.92 (m, 1H), 2.78 (t, J = 6.8 Hz, 2H), 2.57 (t, J = 6.8 Hz, 2H), 1.28 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 404.1 (M+H) ⁺ . [0954] Step 7: Synthesis of 2-(3-Amino-3-oxopropyl)-N-(4-cyano-7-(4- isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)oxirane-2-carbox amide [0955] To a mixture of N ¹ -(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzofuran- 5-yl)- 2-methylenepentanediamide (650 mg, 1.61 mmol) in DCM (13 mL) was added 30% H2O2 (0.65 mL, 6.44 mmol) and TFAA (1.14 mL, 8.06 mmol). Then the mixture was stirred at room temperature for 16 hours. The mixture was quenched with water (100 mL) and extracted with EtOAc (200 mL × 3). The organic layer was washed with water (100 mL × 3), dried over Na2SO4, filtered and concentrated. The mixture was purified by prep-HPLC (Boston Uni C18 40*150*5um, water (0.2%FA)-ACN, 42-72%) to afford the title compound (200 mg, 30%) as a white solid. LCMS (ESI): m/z 420.2 (M+H) ⁺ . [0956] Step 8: Preparation of (R)-2-(3-Amino-3-oxopropyl)-N-(4-cyano-7-(4- isopropylphenyl)-2,3-dihydrobenzofuran-5-yl)oxirane-2-carbox amide and (S)-2-(3-amino-3- oxopropyl)-N-(4-cyano-7-(4-isopropylphenyl)-2,3-dihydrobenzo furan-5-yl)oxirane-2- carboxamide [0957] 2-(3-Amino-3-oxopropyl)-N-(4-cyano-7-(4-isopropylphenyl)-2,3 - dihydrobenzofuran-5-yl)oxirane-2-carboxamide (200 mg, 0.48 mmol) was separated by SFC (DAICEL CHIRALCEL OD-H (250mm*30mm,5um), 0.1% NH ₃ H ₂ O, MEOH, 45-45%) to afford a first-eluting Enantiomer A (64.38 mg, 29%) as a white solid and a second-eluting Enantiomer B (45.25 mg, 21%) as a white solid. [0958] Enantiomer A: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.35 (s, 1H), 7.88 (s, 1H), 7.64 (d, J = 6.8 Hz, 2H), 7.31 (d, J = 6.8 Hz, 2H), 5.72 (s, 1H), 5.32 (s, 1H), 4.74 (t, J = 8.8 Hz, 2H), 3.45 (t, J = 8.8 Hz, 2H), 3.13 - 3.07 (m, 2H), 3.00 - 2.90 (m, 1H), 2.72 - 2.62 (m, 1H), 2.59 - 2.49 (m, 2H), 2.13 - 2.01 (m, 1H), 1.28 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 420.1 (M+H) ⁺ . [0959] Enantiomer B: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.35 (s, 1H), 7.88 (s, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 5.73 (s, 1H), 5.31 (s, 1H), 4.74 (t, J = 8.8 Hz, 2H), 3.45 (t, J = 8.8 Hz, 2H), 3.13 - 3.07 (m, 2H), 3.00 - 2.90 (m, 1H), 2.72 - 2.62 (m, 1H), 2.59 - 2.49 (m, 2H), 2.13 - 2.01 (m, 1H), 1.28 (d, J = 6.8 Hz, 6H); LCMS (ESI): m/z 420.1 (M+H) ⁺ . EXAMPLE 53 [0960] Preparation of N-(4-(Hydroxymethyl)-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-5-yl)acrylamide [0961] The general reaction scheme was as follows: [0962] Step 1: Preparation of Methyl 5-amino-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-4-carboxylate [0963] A solution of methyl 5-amino-7-chloro-2,3-dihydrobenzofuran-4-carboxylate (196 mg, 0.86 mmol), (4-(trifluoromethoxy)phenyl)boronic acid (177 mg, 0.86 mmol), Xphos Pd G2 (72 mg, 0.09 mmol), Xphos (40 mg, 0.09 mmol) and KOAc (254mg, 2.58 mmol) in 1,4- dioxane (5 mL) and water (0.50 mL) was stirred at 80°C for 3 hours under an N ₂ atmosphere. The reaction solution was quenched with water (50 mL), extracted with EtOAc (50 mL × 2). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by prep-TLC (30% ethyl acetate in petroleum ether) to afford the title compound (250 mg, 66%) as a green oil. LCMS (ESI): m/z 353.9 (M+H) ⁺ . [0964] Step 2: Preparation of (5-Amino-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-4-yl)methanol [0965] To a solution of methyl 5-amino-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-4-carboxylate (250 mg, 0.57 mmol) in THF (4 mL) was added LiAlH ₄ (64 mg, 1.7 mmol) at 0°C. Then the reaction mixture was stirred at 0°C for 1 hour. The mixture was quenched by water (1 mL), 1 M NaOH solution (1 mL), dried over MgSO4, filtered and concentrated. The residue was purified by prep-TLC (50% ethyl acetate in petroleum ether) to afford the title compound (150 mg, 82%) as a white solid. LCMS (ESI): m/z 326.1 (M+H) ⁺ . [0966] Step 3: Preparation of (5-Acrylamido-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-4-yl)methyl acrylate [0967] To a solution of (5-amino-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-4-yl)methanol (100 mg, 0.31 mmol) and DIPEA (0.08 mL, 0.46 mmol) in DCM (2 mL) was cooled to -78 °C and acryloyl chloride (0.04 mL, 0.62 mmol) was added while maintain the temperature at -78°C. The resulting mixture was stirred at -78°C for 1 hour. The reaction was then quenched by water (1 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by prep-HPLC (Boston Green ODS 150*30mm*5um, water(0.225%FA)- CAN, 65-95%) to afford the title compound (40 mg, 30%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 9.73 (s, 1 H), 7.78 (d, J = 8.8 Hz, 2H), 7.43 (d, J = 8.8 Hz, 2H), 7.36 (s, 1 H), 6.47 (d, J = 16.8, 10.4 Hz, 1H), 6.33 (dd, J = 16.4, 1.6 Hz, 1H), 6.25 - 6.13 (m, 2H), 5.95 (dd, J = 10.4, 1.6 Hz, 1H), 5.75 (dd, J = 10.4, 1.6 Hz, 1H), 5.12 (s, 2H), 4.63 (t, J = 8.8 Hz, 2H). [0968] Step 4: N-(4-(Hydroxymethyl)-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-5-yl)acrylamide [0969] To a solution of (5-acrylamido-7-(4-(trifluoromethoxy)phenyl)-2,3- dihydrobenzofuran-4-yl)methyl acrylate (40 mg, 0.10 mmol) in THF (1 mL) was added an aq. 1M lithium hydroxide monohydrate (1 mL). The reaction mixture was stirred at room temperature for 2 hours. The residue was purified by prep-HPLC (Boston Green ODS 150*30mm*5um, water (0.225%FA)-CAN, 45-75%) to afford the title compound (9.07 mg, 24%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ 9.61 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.51 (s, 1H), 7.43 (d, J = 8.0 Hz, 2H), 6.47 (dd, J = 17.2, 10.0 Hz, 1H), 6.21 (dd, J = 17.2, 2.0 Hz, 1H), 5.71 (dd, J = 10.0, 2.0 Hz, 1H), 5.12 (t, J = 5.2 Hz, 1H), 4.62 (t, J = 8.8 Hz, 2H), 4.46 (d, J = 5.2 Hz, 2H), 3.31 (d, J = 8.8 Hz, 2H); LCMS (ESI): m/z 362.0 (M-H2O+H) ⁺ . EXAMPLE 54 [0970] Preparation of N-[4-(Hydroxymethyl)-7-[4-(pentafluoro-6-sulfanyl)phenyl]-2, 3- dihydrobenzofuran-5-yl]prop-2-enamide [0971] The general reaction scheme was as follows: [0972] Step 1: Preparation of Methyl 5-amino-7-[4-(pentafluoro-6-sulfanyl)phenyl]-2,3- dihydrobenzofuran-4-carboxylate [0973] To a solution of Xphos Pd G2 (81 mg, 0.10 mmol), KOAc (285 mg, 2.90 mmol), methyl 5-amino-7-chloro-2,3-dihydrobenzofuran-4-carboxylate (220 mg, 0.97 mmol), pentafluoro-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl]-6-sulfane (383 mg, 1.16 mmol) and Xphos (45 mg, 0.10 mmol) in 1,4-dioxane (5 mL) and water (0.5 mL) was stirred at 80°C for 3 hours under N2 atmosphere. The reaction solution was diluted with water (20 mL) and extracted with ethyl acetate (20 mL × 3).The organics were washed with brine (10mL × 2), dried over sodium sulfate, filtered and concentrated. The residue was purified by pre-TLC (50% DCM in petroleum ether) to afford the title compound (130 mg, 34%) as a green oil. ¹ H NMR (400 MHz, CDCl3): δ 7.82 - 7.76 (m, 4H), 6.63 (s, 1H), 5.41 (s, 2H), 4.56 (t, J = 8.8 Hz, 2 H), 3.91 (s, 3 H), 3.52 (d, J = 8.8 Hz, 2 H); LCMS (ESI): m/z 396.0 (M+H) ⁺ . [0974] Step 2: Preparation of [5-Amino-7-[4-(pentafluoro-6-sulfanyl)phenyl]-2,3- dihydrobenzofuran-4-yl]methanol [0975] To a solution of methyl 5-amino-7-[4-(pentafluoro-6-sulfanyl)phenyl]-2,3- dihydrobenzofuran-4-carboxylate (130 mg, 0.33 mmol) in THF (2 mL) was added LiAlH4 (38 mg, 0.99 mmol) at 0°C. Then the reaction mixture was stirred at 0 ^o C for 1 hour. The mixture was quenched by water (1 mL), 1M aq. NaOH (1 mL) and water (1 mL), dried over MgSO ₄ , the mixture was filtered and concentrated. The residue was purified by pre-TLC (30% ethyl acetate in petroleum ether) to afford the title compound (70 mg, 58%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.80 - 7.74 (m, 4H), 6.68 (s, 1H), 4.73 (s, 2H), 4.60 (t, J = 8.8 Hz, 2H), 3.26 (t, J = 8.8 Hz, 2 H); LCMS (ESI): m/z 368.0 (M+H) ⁺ . [0976] Step 3: Preparation of N-[4-(Hydroxymethyl)-7-[4-(pentafluoro-6- sulfanyl)phenyl]-2,3-dihydrobenzofuran-5-yl]prop-2-enamide [0977] To a solution of [5-amino-7-[4-(pentafluoro-6-sulfanyl)phenyl]-2,3- dihydrobenzofuran-4-yl]methanol (70 mg, 0.19 mmol) in DCM (2 mL) was added DIPEA (0.05 mL, 0.29 mmol) and acryloyl chloride (0.02 mL, 0.19 mmol) at -78 ^o C. The mixture was stirred at -78 ^o C for 1 hour. The reaction was diluted with water (10 mL) and extracted with dichloromethane (30 mL × 3). The organics were washed with brine (20 mL × 2), dried over sodium sulfate, filtered and concentrated. The residue was purified by prep-TLC (50% ethyl acetate in petroleum ether) to afford the title compound (6.81 mg, 9%) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 9.63 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.58 (s, 1H), 6.49 (dd, J = 16.8, 10.0 Hz, 1H), 6.23 (dd, J = 16.8, 2.0 Hz, 1H), 5.75 (dd, J = 10.0, 2.0 Hz, 1H), 5.14 (t, J = 5.2 Hz, 1H), 4.65 (t, J = 8.8 Hz, 2H), 4.47 (d, J = 5.2 Hz, 2H), 3.30 (t, J = 8.8 Hz, 2H); LCMS (ESI): m/z 444.1 (M+Na) ⁺ . [0978] EXAMPLE 55 [0979] Preparation of N-(7-Cyano-4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazol-6- yl)acrylamide [0980] The general reaction scheme was as follows: [0981] Step 1: Preparation of 4-Bromo-6-nitrobenzo[d]thiazole [0982] To a solution of 6-nitrobenzo[d]thiazole (10.0 g, 55.5 mmol) in H ₂ SO ₄ (50 mL) was added NBS (10.87 g, 61.05 mmol) at 0 °C. Then the mixture was stirred at 60 °C for 5 hours. The mixture was quenched with water (500 mL) and extracted with EtOAc (1 L × 3). The organic layer was washed with water (500 mL × 3), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was washed by EtOAc (50 mL) to afford the title compound (10 g, 69%) as a white solid. ¹ H NMR (400 MHz, CDCl3): δ 9.37 (s, 1H), 8.89 (d, J = 2.0 Hz, 1H), 8.64 (d, J = 2.0 Hz, 1H). [0983] Step 2: Preparation of 6-Nitro-4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazole [0984] A mixture of 4-bromo-6-nitrobenzo[d]thiazole (4.90 g, 18.91 mmol), (4- (trifluoromethoxy)phenyl)boronic acid (4.67 g, 22.7 mmol), Pd(dppf)Cl ₂ (1.38 g, 1.89 mmol) and K ₂ CO ₃ (7.84 g, 56.74 mmol) in 1,4-dioxane (50 mL) and water (5 mL) was stirred at 100°C for 2 hours under a N2 atmosphere. The reaction mixture was then concentrated under vacuum. The residue was purified by flash chromatography on silica gel (0 - 25% ethyl acetate in petroleum ether ) to afford the title compound (5.0 g, 78%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 9.32 (s, 1H), 8.92 (d, J = 2.4 Hz, 1H), 8.48 (d, J = 2.4 Hz, 1H), 7.94 - 7.13 (m, 2H), 7.41 (d, J = 8.0 Hz, 2H); LCMS (ESI): m/z 341.0 (M+H) ⁺ . [0985] Step 3: Preparation of 4-(4-(Trifluoromethoxy)phenyl)benzo[d]thiazol-6-amine [0986] A solution of 6-nitro-4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazole (5.0 g, 14.69 mmol) and 10% Pd/C (1.56 g, 14.69 mmol) in ethanol (100 mL) under H2 (15 psi) was stirred at room temperature for 16 hours. The reaction mixture was filtered and concentrated to afford the title compound (4.2 g, 92%) as a yellow solid. ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.75 (s, 1H), 7.84 - 7.81 (m, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 2.4 Hz, 1H), 6.93 (d, J = 2.4 Hz, 1H), 3.93 (s, 2H); LCMS (ESI): m/z 311.0 (M+H) ⁺ . [0987] Step 4: Preparation of 7-Bromo-4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazol- 6-amine [0988] A solution of 4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazol-6-amine (4.2 g, 13.54 mmol) and NBS (2.41 g, 13.54 mmol) in DCM (50 mL) was stirred at 0 °C for 1 hour. The residue was purified by flash chromatography on silica gel eluting with (0 - 25% ethyl acetate in petroleum ether) to afford the title compound (3.8 g, 72%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 8.79 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.00 (s, 1H), 4.31 (s, 2H); LCMS (ESI): m/z 389.0 (M+H) ⁺ . [0989] Step 5: Preparation of 6-Amino-4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazole- 7-carbonitrile [0990] A mixture of 7-bromo-4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazol-6-amin e (2.0 g, 5.14 mmol), t-BuXphos Pd G ₃ (408 mg, 0.51 mmol) and Zn(CN) ₂ (3.02 g, 25.69 mmol) in DMA (20 mL) was stirred at 135 °C for 16 hours under N ₂ atmosphere. The reaction solution was quenched with water (200 mL), extracted with EtOAc (200 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (0 - 25 % ethyl acetate in petroleum ether) to afford the title compound (1.3 g, 75%) as a yellow solid. ¹ H NMR (400 MHz, CDCl3): δ 8.82 (s, 1H), 7.85 - 7.78 (m, 2H), 7.36 (d, J = 8.4 Hz, 2H), 6.93 (s, 1H), 4.74 (s, 2H); LCMS (ESI): m/z 335.9 (M+H) ⁺ . [0991] Step 6: Preparation of N-(7-Cyano-4-(4- (trifluoromethoxy)phenyl)benzo[d]thiazol-6-yl)acrylamide [0992] To a mixture of 6-amino-4-(4-(trifluoromethoxy)phenyl)benzo[d]thiazole-7- carbonitrile (120 mg, 0.36 mmol) and DIPEA (0.12 mL, 0.72 mmol) in DCM at 0 °C was added acryloyl chloride (0.06 mL, 0.72 mmol). Then the reaction was stirred at 0 °C for 1 hour. The reaction solution was quenched with water (2 mL), dried over MgSO4, filtered and concentrated. The residue was purified by prep-HPLC (Boston Green ODS 150*30mm*5um, water(0.225%FA)-CAN, 58-88%) to afford the title compound (29.43 mg, 21%) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 10.82 (s, 1H), 9.57 (s, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.94 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 6.60 (dd, J = 16.8, 10.4 Hz, 1H), 6.37 (dd, J = 16.8, 1.2 Hz, 1H), 5.91 (d, J = 10.4, 1.2 Hz, 1H); LCMS (ESI): m/z 389.9 (M+H) ⁺ . EXAMPLE 56 [0993] His-tagged TEAD proteins are pre-incubated with TEAD project compounds for 30 minutes at room temperature. Biotinylated lipid pocket probes are then added to the TEAD/Compound mixture and incubated for 60 minutes at room temperature. The lipid pocket probe competes with the test compound for the TEAD lipid pocket until equilibrium is reached. After 60 minutes, Europium labelled anti-His (Perkin Elmer # AD0110) and XL665 labelled streptavidin (CIS Bio 610SAXAC) are added to the TEAD/test compound/lipid pocket mixture and incubated for 30 minutes. TR-FRET values are then measured using an EnVision multi-label plate reader (Perkin Elmer Cat# 2104-0010A.) If the lipid pocket probe binds to TEAD as expected, a TR-FRET signal results from the proximity of anti-His Eu and XL665. If a TEAD lipid pocket binder such as binds and displaces the lipid pocket probe, the disruption of the TEAD:probe interaction results in a decrease in TR-FRET signal. The potency of compounds as TEAD lipid pocket binders is determined by IC50 value generated using a non-linear 4 parameter curve fit. This assay format enables more sensitive determinations of lipid pocket affinity than the aforementioned TEAD lipid pocket FP assay due to the decreased concentration of TEAD protein required for the TR-FRET assay format. [0994] The results for compounds from Examples 1-51 are presented in Table 2 below. Table 2 EXAMPLE 57 [0995] His-tagged TEAD2 or 4 proteins are pre-incubated with TEAD project compounds for 4 hours at room temperature. Biotinylated lipid pocket probes are then added to the TEAD/Compound mixture and incubated for 60 minutes at room temperature. The lipid pocket probe competes with the test compound for the TEAD lipid pocket until equilibrium is reached. After 60 minutes, Europium labelled anti-His (Perkin Elmer # AD0110) and XL665 labelled streptavidin (CIS Bio 610SAXAC) are added to the TEAD/test compound/lipid pocket mixture and incubated for 30 minutes. TR-FRET values are then measured using an EnVision multi-label plate reader (Perkin Elmer Cat# 2104-0010A.) If the lipid pocket probe binds to TEAD as expected, a TR-FRET signal results from the proximity of anti-His Eu and XL665. If a TEAD lipid pocket binder such as binds and displaces the lipid pocket probe, the disruption of the TEAD:probe interaction results in a decrease in TR-FRET signal. The potency of compounds as TEAD lipid pocket binders is determined by IC50 value generated using a non-linear 4 parameter curve fit. [0996] The results for compounds from Examples 53-55 are presented in Table 4 below. Table 3 [0997] This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims. [0998] It is to be understood that the invention is not limited to the particular embodiments and aspects of the disclosure described above, as variations of the particular embodiments and aspects may be made and still fall within the scope of the appended claims. All documents cited to or relied upon herein are expressly incorporated by reference.