Patent Publication Number: US-2023146125-A1

Title: Forms and compositions of inhibitors of jak2

Description:
RELATED APPLICATIONS 
     This application claims priority to and benefit of U.S. Application No. 63/277,419, filed Nov. 9, 2021, the entire contents of which are hereby incorporated by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     Janus kinase 2 (JAK2) is a non-receptor tyrosine kinase involved in the JAK-STAT signaling pathway, which plays a role in cell processes such as immunity, cell division, and cell death. Dysfunction of the JAK-STAT pathway is implicated in various diseases, including cancer and other proliferative diseases, as well as diseases of the immune system. For example, essentially all BCR-ABL1-negative myeloproliferative neoplasms are associated with mutations that activate JAK2. In particular, JAK2V617F is the most prevalent mutation in myeloproliferative neoplasms, occurring in approx. 70% of all patients, and in up to 95% of patients with polycythemia vera. (Vainchenker, W., Kralovics, R. Blood 2017, 129(6):667-79). Even less common mutations, such as in MPL and CALR, have been shown to effect activation of JAK2, thereby initiating and/or driving disease progression. (Vainchenker, W. et al., F1000Research 2018, 7 (F1000 Faculty Rev): 82). Furthermore, polymorphisms in JAK2 have been linked to various autoimmune diseases and inflammatory conditions, such as psoriasis and inflammatory bowel disease. (O&#39;Shea, J. J. et al., Ann. Rheum. Dis. 2013 April, 72:ii111-ii115). Increased signaling through JAK2, as well as other members of the JAK family, is also associated with atopic dermatitis. (Rodrigues, M. A. and Torres, T. J. Derm. Treat. 2019, 31(1):33-40). 
     Inhibitors of JAKs (e.g., JAK2) are classified based on their binding mode. All currently approved JAK inhibitors are Type I inhibitors, which are those that bind the ATP-binding site in the active conformation of the kinase domain, thereby blocking catalysis (Vainchenker, W. et al.). However, increased phosphorylation of the JAK2 activation loop is observed with Type I inhibitors and may lead to acquired resistance in certain patients (Meyer S. C., Levine, R. L. Clin. Cancer Res. 2014, 20(8):2051-9). Type II inhibitors, on the other hand, bind the ATP-binding site of the kinase domain in the inactive conformation and, therefore, may avoid hyperphosphorylation observed with Type I inhibitors (Wu, S. C. et al. Cancer Cell 2015 Jul. 13, 28(1):29-41). 
     Chemical compounds can form one or more different pharmaceutically acceptable salts and/or solid forms, including amorphous and polymorphic crystal forms. Individual salts and solid forms of bioactive chemical compounds can have different properties. There is a need for the identification and selection of appropriate salts and/or solid forms of bioactive chemical compounds (including appropriate crystalline forms, where applicable) for the development of pharmaceutically acceptable dosage forms for the treatment of various diseases or conditions associated with JAK2. 
     SUMMARY OF THE INVENTION 
     The present disclosure provides novel salts and solid forms useful as inhibitors of JAK2. In general, salt forms or free base forms, and pharmaceutically acceptable compositions thereof, are useful for treating or lessening the severity of a variety of diseases or disorders as described in detail herein. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    provides a X-ray powder diffraction (XRPD) pattern of Compound 1 Form 1 (free base). 
         FIG.  2    provides a DVS isotherm plot of Compound 1 Form 1 (free base). 
         FIG.  3    depicts a XRPD overlay of Compound 1 Form 1 post-DVS material (lower) with pre-DVS material (upper). 
         FIG.  4    provides a X-ray powder diffraction (XRPD) pattern of Compound 2 Form A. 
         FIG.  5    provides TGA (top)/DSC (bottom) curves for Compound 2 Form A. 
         FIG.  6    provides a DVS isotherm plot of Compound 2 Form A. 
         FIG.  7    depicts a XRPD overlay of Compound 2 Form A post-DVS material (lower) with pre-DVS material (upper). 
         FIG.  8    provides a X-ray powder diffraction (XRPD) pattern of Compound 3 Form A. 
         FIG.  9    provides TGA (top)/DSC (bottom) curves for Compound 3 Form A. 
         FIG.  10    provides a X-ray powder diffraction (XRPD) pattern of Compound 4 Form A. 
         FIG.  11    provides TGA (top)/DSC (bottom) curves for Compound 4 Form A. 
         FIG.  12    provides a X-ray powder diffraction (XRPD) pattern of Compound 4 Form B. 
         FIG.  13    provides X-ray powder diffraction (XRPD) pattern of Compound 5 Form C. 
         FIG.  14 A  provides XRPD spectra of three lots of Compound 1. From top to bottom: Compound 1 Lot I, Compound 1 Lot 11, and Compound 1 Lot III.  FIG.  14 B  provides a magnified view of the spectra from  FIG.  14 A  between approx. 6.7 and 8.5 degrees 2-theta. Characteristic peak for each of Form A, Form B, and Form O of Compound 1 is labeled. 
         FIG.  15    provides a DVS isotherm plot of a sample from Compound 1 Lot II. 
         FIG.  16    depicts a XRPD overlay of Compound 1 Lot II post-DVS material (lower) with pre-DVS material (upper). 
         FIG.  17    provides TGA (top)/DSC (bottom) curves for Compound 1 Lot III. 
         FIG.  18 A  depicts an XRPD overlay of Compound 1 Forms. From top to bottom; Form A, Form B, Form C, Form D, Form E.  FIG.  18 B  depicts an XRPD overlay of Compound 1 Forms. From top to bottom: Form F, Form G, Form H, Form J, Form K.  FIG.  18 C  depicts an XRPD overlay of Compound 1 Forms. From top to bottom: Form L, Form M, Form N, Form O+minor Form B, Form P. 
         FIG.  19    provides a XRPD pattern of Compound 1 Form A. 
         FIG.  20    provides TGA (top)/DSC (bottom) curves for Compound 1 Form A. 
         FIG.  21    provides TGA (top)/DSC (bottom) curves for Compound 1 Form B. 
         FIG.  22    provides a XRPD pattern of Compound 1 Form B. 
         FIG.  23    provides a XRPD pattern of Compound 1 Form C. 
         FIG.  24    provides TGA (top)/DSC (bottom) curves for Compound 1 Form C. 
         FIG.  25    provides a XRPD pattern of Compound 1 Form D. 
         FIG.  26    provides TGA (top)/DSC (bottom) curves for Compound 1 Form D. 
         FIG.  27    provides a XRPD pattern of Compound 1 Form E. 
         FIG.  28    provides a XRPD pattern of Compound 1 Form H. 
         FIG.  29    provides a XRPD pattern of Compound 1 Form F. 
         FIG.  30    provides TGA (top)/DSC (bottom) curves for Compound 1 Form F. 
         FIG.  31    provides a XRPD pattern of Compound 1 Form G. 
         FIG.  32    provides a XRPD pattern of Compound 1 Form J. 
         FIG.  33    provides a XRPD pattern of Compound 1 Form K. 
         FIG.  34    provides a XRPD pattern of Compound 1 Form L. 
         FIG.  35    provides a XRPD pattern of Compound 1 Form M. 
         FIG.  36    provides a XRPD pattern of Compound 1 Form N. 
         FIG.  37    provides TGA (top)/DSC (bottom) curves for Compound 1 Form N. 
         FIG.  38    provides a XRPD pattern of Compound 1 Form P. 
         FIG.  39    depicts a series of XRPD spectra obtained in a variable relative humidity (VRH)-XRPD experiment of Form A. From top to bottom: ambient RH (˜30%); ˜21% RH; ˜15% RH; ˜11% RH; ˜7% RH; ˜5% RH. Characteristic peak for each of Form A and Form B of Compound 1 is labeled. 
         FIG.  40    provides an overlay of XRPD spectra of Form A before (top) and after exposure to a nitrogen stream for 17 h (bottom), whereby it has converted to Form B. 
         FIG.  41    provides a series of XRPD spectra obtained in a VRH-XRPD experiment of Form B. From top to bottom: ˜53% RH; ˜62% RH; ˜61% RH; ˜61% RH. 
         FIG.  42    is a schematic presentation of both VRH-XRPD experiments, plotting Form A/Form B ratios versus average RH values. 
         FIG.  43    is a schematic presentation of the results from certain polymorph screening experiments described herein. 
     
    
    
     DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS 
     The compound N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-11H-imidazo[4,5-h]pyridin-6-yl)oxy)pyridin-2-yl)acetamide: 
     
       
         
         
             
             
         
       
     
     is a small molecule inhibitor of JAK2. The present disclosure provides various free base and salt forms of Compound 1, solid forms thereof, pharmaceutical compositions thereof, and methods of preparing those novel free base and salt forms of Compound 1 and solid forms thereof. 
     Compound 1 has shown potency against JAK2 in an in vitro assay. Accordingly, Compound 1 is useful for treating diseases, disorders, or conditions associated with JAK2. 
     The present disclosure provides various free base solid forms of Compound 1, salt forms of Compound 1 and solid forms thereof, pharmaceutical compositions thereof, and methods of preparing solid forms of Compound 1 and salts and solid forms thereof. Salt forms and solid forms (e.g., crystalline solid forms) impart or may impart characteristics such as improved aqueous solubility, stability, hygroscopicity (e.g., provided forms may be less hygroscopic than another form), absorption, bioavailability, and ease of formulation. 
     As used herein, unless otherwise indicated the term “salt” refers to a salt or co-crystal of two or more (e.g., two) component molecules (e.g., Compound 1 and a co-former). In the combination of an acid and a base compound for the preparation of a solid form, a Δ pK a  (pK a (base)−pK a (acid))≥1 generally will permit the formation of a salt compound where the two compounds are ionized. Where this threshold is not met, non-ionic interactions (e.g., hydrogen bonds) can still occur between neutral acid and the base compounds to form, e.g., a co-crystal. In some embodiments, a provided solid form is a salt. In other embodiments, a provided solid form is a co-crystal. 
     It will be appreciated that a crystalline solid form of Compound 1 or a salt thereof may exist in a neat (i.e., unsolvated) form, a hydrated form, a solvated form, and/or a heterosolvated form. In some embodiments, a crystalline solid form of Compound 1 or a salt thereof does not have any water or other solvent incorporated into the crystal lattice (i.e., is “unsolvated” or an “anhydrate”). In some embodiments, a crystalline solid form of Compound 1 or a salt thereof comprises water and/or other solvent in the crystal lattice (i.e., are hydrates and/or solvates, respectively). It will be appreciated that solvates comprising only certain solvents (most notably, water) are suitable for development as a drug. Solvates comprising other solvents may be useful for manufacturing and/or testing, inter alia, even if they may not be acceptable for use in an approved therapeutic product. 
     Without wishing to be bound by any particular theory, it was initially believed that salt forms of Compound 1 (e.g., Compounds 2-5) would be advantageous (e.g., improved aqueous solubility, stability, hygroscopicity, absorption, bioavailability, ease of formulation) as compared to free base solid forms of Compound 1. It will be appreciated that, in some embodiments, it is desirable for compound salt forms to not be prone to disproportionation, e.g., upon storage, in the presence of excipients, and/or when stirred in a solvent (e.g., water) for a period of time, particularly if such salt forms are to be used in a pharmaceutical product. The present disclosure encompasses the recognition that i) certain salt forms of Compound 1 possess properties (e.g., lower solubility and/or propensity for disproportionation) that may render them less favorable for use as pharmaceutical product, and ii) that certain crystalline free base solid forms of Compound 1 unexpectedly possess properties (e.g., stability, solubility, ease of formulation, and/or hygroscopicity) that render them more favorable for use as a pharmaceutical product as compared with other free base solid forms of Compound 1 or salts thereof. As described herein, in some embodiments, certain provided free base forms of Compound 1 are preferred over certain provided salt forms, because certain salt forms are prone to disproportionation. For example, as described in Example 11 herein, Compound 1 Form A can be prepared via a disproportionation reaction of Compound 2, demonstrating a superior stability of Compound 1 Form A over Compound 2. 
     Without wishing to be bound by any particular theory, the present disclosure recognizes certain challenges in obtaining free base solid forms of Compound 1 in a consistent manner, as well as provides a solution to this problem. As described in Example 9, despite using similar methods of synthesis and purification, different lots of Compound 1 comprised different free base forms and mixtures thereof. The present disclosure provides methods of preparing Compound 1 free base forms that are substantially free of impurities and/or other free base forms, and that reproducibly provide the same polymorphic form. For example, a process for preparing Compound 1 Form A is described in Example 11, and a process for preparing Compound 1 Form N is described in Example 21. 
     I. Free Base Forms of Compound 1 
     1. Compound 1 
     It is contemplated that Compound 1 can exist in a variety of physical forms. For example, Compound 1 can be in solution, suspension, or in solid form. In certain embodiments, Compound 1 is in solid form. When Compound 1 is in solid form, said compound may be amorphous, crystalline, or a mixture thereof. Exemplary solid forms are described in more detail below. 
     In some embodiments, the present disclosure provides a form of Compound 1 substantially free of impurities. As used herein, the term “substantially free of impurities” means that the compound contains no significant amount of extraneous matter. Such extraneous matter may include different forms of Compound 1, residual solvents, or any other impurities that may result from the preparation of, and/or isolation of, Compound 1. In certain embodiments, at least about 95% by weight of a form of Compound 1 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of a form of Compound 1 is present. In still other embodiments of the disclosure, at least about 99% by weight of a form of Compound 1 is present. 
     The terms “about” and “approximately”, unless otherwise stated and when used herein in reference to a value, refers to a value that is similar, in context to the referenced value. In general, those skilled in the art, familiar with the context, will appreciate the relevant degree of variance encompassed by about/approximately in that context. Unless otherwise stated, in some embodiments the term “about” or “approximately” may encompass a range of values that within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would be less than 0%, or would exceed 100% of a possible value). 
     According to one embodiment, a form of Compound 1 is present in an amount of at least about 97.0, 97.5, 98.0, 98.5, 99.0, 99.5, or 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, a form of Compound 1 contains no more than about 3.0 area percent HPLC of total organic impurities and, in certain embodiments, no more than about 1.5 area percent HPLC total organic impurities relative to the total area of the HPLC chromatogram. In other embodiments, a form of Compound 1 contains no more than about 1.0 area percent HPLC of any single impurity; no more than about 0.6 area percent HPLC of any single impurity, and, in certain embodiments, no more than about 0.5 area percent HPLC of any single impurity, relative to the total area of the HPLC chromatogram. 
     The structure depicted for a form of Compound 1 is also meant to include all tautomeric forms of Compound 1. Additionally, structures depicted here are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a  13 C- or  14 C-enriched carbon are within the scope of this disclosure. 
     It has been found that Compound 1 can exist in a variety of solid forms. 
     In some embodiments, Compound 1 is amorphous. In some embodiments, Compound 1 is amorphous, and is substantially free of crystalline Compound 1. As used herein, the term “substantially free of crystalline Compound 1” means that the compound contains no significant amount of crystalline Compound 1. In some embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of amorphous Compound 1 is present. In some embodiments, at least about 99% by weight of amorphous Compound 1 is present. 
     In certain embodiments, Compound 1 is a crystalline solid. In some embodiments, Compound 1 is a crystalline solid substantially free of amorphous Compound 1. As used herein, the term “substantially free of amorphous Compound 1” means that the compound contains no significant amount of amorphous Compound 1. In certain embodiments, at least about 95% by weight of crystalline Compound 1 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of crystalline Compound 1 is present. In still other embodiments of the disclosure, at least about 99% by weight of crystalline Compound 1 is present. 
     In some embodiments, Compound 1 is provided as a particular crystalline form that is substantially free of other crystalline forms of Compound 1. For example, in some embodiments, a composition comprises Compound 1 Form A substantially free of other crystalline forms of Compound 1 (e.g., Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form J, Form K, Form L, Form M, Form N, Form O, and/or Form P). As used herein, the term “substantially free of other crystalline forms of Compound 1” means that the compound contains no significant amount of other crystalline forms of Compound 1. In some embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of a particular crystalline form (e.g., Form A) of Compound 1 is present. In some embodiments, at least about 99% by weight of a particular crystalline form (e.g., Form A) of Compound 1 is present. 
     Compound 1 Form 1 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form 1. In some embodiments, Compound 1 is in Form 1, substantially free from other free base forms of Compound 1. It will be appreciated that, in some embodiments, “Compound 1 Form 1” describes a mixture of one or more forms of Compound 1 (e.g., Compound 1 Form A and Compound 1 Form B, as described herein). 
     In some embodiments, Compound 1 Form 1 has at least 1, 2, 3, 4 or 5 X-ray Powder Diffraction (XRPD) peaks selected from the angles (degrees 2 theta±0.20) listed in Table 1 below. 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 XRPD Peak Positions for Compound 1 Form 1 
               
               
                 Angle/° 2θ 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 6.18 
               
               
                 6.70 
               
               
                 7.33 
               
               
                 8.04 
               
               
                 8.77 
               
               
                 9.10 
               
               
                 9.59 
               
               
                 9.78 
               
               
                 10.31 
               
               
                 11 22 
               
               
                 11.46 
               
               
                 12.07 
               
               
                 12.32 
               
               
                 12.98 
               
               
                 14.01 
               
               
                 15.34 
               
               
                 15.62 
               
               
                 15.85 
               
               
                 16.62 
               
               
                 16.89 
               
               
                 17.59 
               
               
                 18.04 
               
               
                 18.19 
               
               
                 18.94 
               
               
                 19.70 
               
               
                 20.08 
               
               
                 20.62 
               
               
                 21.36 
               
               
                 21.71 
               
               
                 22.22 
               
               
                 22.87 
               
               
                 23.31 
               
               
                 23.56 
               
               
                 24.09 
               
               
                 25.22 
               
               
                 26.20 
               
               
                 26.58 
               
               
                 27.29 
               
               
                   
               
            
           
         
       
     
     In some embodiments, Compound 1 Form 1 is characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (degrees 2 theta±0.20) and corresponding d-spacing of: 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 XRPD Peak Positions and d-Spacing for Compound 1 Form 1 
               
            
           
           
               
               
               
            
               
                   
                 Angle/° 2θ 
                 d-spacing/Angstrom 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 6.18 
                 14.301 ± 0.463  
               
               
                   
                 6.70 
                 13.174 ± 0.393  
               
               
                   
                 7.33 
                 12.045 ± 0.328  
               
               
                   
                 8.04 
                 10.985 ± 0.273  
               
               
                   
                 8.77 
                 10.080 ± 0.230  
               
               
                   
                 9.10 
                 9.708 ± 0.213 
               
               
                   
                 9.59 
                 9.212 ± 0.192 
               
               
                   
                 9.78 
                 9.035 ± 0.184 
               
               
                   
                 10.31 
                 8.570 ± 0.166 
               
               
                   
                 11.22 
                 7.880 ± 0.140 
               
               
                   
                 11.46 
                 7.715 ± 0.134 
               
               
                   
                 12.07 
                 7.324 ± 0.121 
               
               
                   
                 12.32 
                 7.181 ± 0.116 
               
               
                   
                 12.98 
                 6.814 ± 0.105 
               
               
                   
                 14.01 
                 6.317 ± 0.090 
               
               
                   
                 15.34 
                 5.770 ± 0.075 
               
               
                   
                 15.62 
                 5.670 ± 0.072 
               
               
                   
                 15.85 
                 5.586 ± 0.070 
               
               
                   
                 16.62 
                 5.330 ± 0.064 
               
               
                   
                 16.89 
                 5.246 ± 0.062 
               
               
                   
                 17.59 
                 5.037 ± 0.057 
               
               
                   
                 18.04 
                 4.914 ± 0.054 
               
               
                   
                 18.19 
                 4.874 ± 0.053 
               
               
                   
                 18.94 
                 4.683 ± 0.049 
               
               
                   
                 19.70 
                 4.503 ± 0.045 
               
               
                   
                 20.08 
                 4.418 ± 0.044 
               
               
                   
                 20.62 
                 4.303 ± 0.041 
               
               
                   
                 21.36 
                 4.156 ± 0.038 
               
               
                   
                 21.71 
                 4.091 ± 0.037 
               
               
                   
                 22.22 
                 3.998 ± 0.036 
               
               
                   
                 22.87 
                 3.886 ± 0.034 
               
               
                   
                 23.31 
                 3.814 ± 0.032 
               
               
                   
                 23.56 
                 3.774 ± 0.032 
               
               
                   
                 24.09 
                 3.691 ± 0.030 
               
               
                   
                 25.22 
                 3.529 ± 0.028 
               
               
                   
                 26.20 
                 3.398 ± 0.025 
               
               
                   
                 26.58 
                 3.351 ± 0.025 
               
               
                   
                 27.29 
                 3.265 ± 0.023 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, Compound 1 Form 1 s characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has two or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has three or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has four or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has five or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has six or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has seven or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has eight or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has nine or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has ten or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has eleven or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has twelve or more peaks in its X-ray powder diffraction pattern selected from those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta. In some embodiments, Compound 1 Form 1 is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58 degrees 2-theta, corresponding to d-spacing shown in Table 2 above. As used herein, the term “about”, when used in reference to a degree 2-theta value refers to the stated value±0.2 degree 2-theta. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form 1 is substantially similar to the XRPD provided in  FIG.  1   . 
     Methods for preparing Compound 1 Form 1 are described infra. 
     Compound 1 Form A 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form A. In some embodiments, Compound 1 Form A is a hydrate. In some embodiments, Compound 1 is provided as Form A, substantially free from other free base forms of Compound 1 (e.g., Compound 1 Form B). 
     In some embodiments, Compound 1 Form A has at least 1, 2, 3, 4 or 5 X-ray Powder Diffraction (XRPD) peaks selected from the angles (degrees 2 theta±0.20) listed in Table A-1 below. 
     
       
         
           
               
             
               
                 TABLE A-l 
               
               
                   
               
               
                 XRPD Peak Positions for Compound 1 Form A 
               
               
                 Angle/° 2θ 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 7.32 
               
               
                 9.57 
               
               
                 9.77 
               
               
                 11.15 
               
               
                 11.45 
               
               
                 12.90 
               
               
                 13.20 
               
               
                 13.99 
               
               
                 14.41 
               
               
                 14.69 
               
               
                 16.39 
               
               
                 16.58 
               
               
                 16.85 
               
               
                 17.24 
               
               
                 17.98 
               
               
                 18.60 
               
               
                 18.95 
               
               
                 19.23 
               
               
                 19.68 
               
               
                 20.23 
               
               
                 20.75 
               
               
                 21.29 
               
               
                 21.68 
               
               
                 22.19 
               
               
                 22.40 
               
               
                 22.93 
               
               
                 23.56 
               
               
                 23.98 
               
               
                 24.51 
               
               
                 25.23 
               
               
                 25.97 
               
               
                 26.60 
               
               
                 27.25 
               
               
                 27.80 
               
               
                 28.78 
               
               
                 29.07 
               
               
                 29.78 
               
               
                 30.70 
               
               
                   
               
            
           
         
       
     
     In some embodiments, Compound 1 Form A is characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (degrees 2 theta±0.20) and corresponding d-spacing of: 
     
       
         
           
               
             
               
                 TABLE A-2 
               
             
            
               
                   
               
               
                 XRPD Peak Positions and d-Spacing for Compound 1 Form A 
               
            
           
           
               
               
               
            
               
                   
                 Angle/° 2θ 
                 d-spacing/Angstrom 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 7.32 
                 12.074 ± 0.330  
               
               
                   
                 9.57 
                 9.238 ± 0.193 
               
               
                   
                 9.77 
                 9.048 ± 0.185 
               
               
                   
                 11.15 
                 7.929 ± 0.142 
               
               
                   
                 11.45 
                 7.723 ± 0.134 
               
               
                   
                 12.90 
                 6.856 ± 0.106 
               
               
                   
                 13.20 
                 6.702 ± 0.101 
               
               
                   
                 13.99 
                 6.325 ± 0.090 
               
               
                   
                 14.41 
                 6.141 ± 0.085 
               
               
                   
                 14.69 
                 6.026 ± 0.082 
               
               
                   
                 16.39 
                 5.404 ± 0.066 
               
               
                   
                 16.58 
                 5,342 ± 0.064 
               
               
                   
                 16.85 
                 5.259 ± 0.062 
               
               
                   
                 17.24 
                 5.138 ± 0.059 
               
               
                   
                 17.98 
                 4.930 ± 0.054 
               
               
                   
                 18.60 
                 4.768 ± 0.051 
               
               
                   
                 18.95 
                 4.678 ± 0.049 
               
               
                   
                 19.23 
                 4.613 ± 0.048 
               
               
                   
                 19.68 
                 4.508 ± 0.045 
               
               
                   
                 20.23 
                 4.385 ± 0.043 
               
               
                   
                 20.75 
                 4.277 ± 0.041 
               
               
                   
                 21.29 
                 4.171 ± 0.039 
               
               
                   
                 21.68 
                 4.096 ± 0.037 
               
               
                   
                 22.19 
                 4.002 ± 0.036 
               
               
                   
                 22.40 
                 3.966 ± 0.035 
               
               
                   
                 22.93 
                 3.875 ± 0.033 
               
               
                   
                 23.56 
                 3.773 ± 0.032 
               
               
                   
                 23.98 
                 3.708 ± 0.030 
               
               
                   
                 24.51 
                 3.628 ± 0.029 
               
               
                   
                 25.23 
                 3.526 ± 0.027 
               
               
                   
                 25.97 
                 3.428 ± 0.026 
               
               
                   
                 26.60 
                 3.348 ± 0.025 
               
               
                   
                 27.25 
                 3.270 ± 0.024 
               
               
                   
                 27.80 
                 3.206 ± 0.023 
               
               
                   
                 28.78 
                 3.099 ± 0.021 
               
               
                   
                 29.07 
                 3.069 ± 0.021 
               
               
                   
                 29.78 
                 2.998 ± 0.020 
               
               
                   
                 30.70 
                 2.910 ± 0.018 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, Compound 1 Form A is characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has two or more peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has three or more peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has four or more peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has five or more peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has six or more peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has seven or more peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has eight or more peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta. In some embodiments, Compound 1 Form A is characterized in that it has peaks in its X-ray powder diffraction pattern selected from those at about 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60 degrees 2-theta, corresponding to d-spacing shown in Table A-2 above. As used herein, the term “about”, when used in reference to a degree 2-theta value refers to the stated value±0.2 degree 2-theta. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form A is substantially similar to the XRPD provided in  FIG.  19   . 
     Methods for preparing Compound 1 Form A are described infra. 
     Compound 1 Form B 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form B. In some embodiments, Compound 1 Form B is anhydrous. In some embodiments, Compound 1 is provided as Form B, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form B is substantially similar to the XRPD provided in  FIG.  22   . 
     Methods for preparing Compound 1 Form B are described infra. 
     Compound 1 Form C 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form C. In some embodiments, Compound 1 Form C is a tri-acetic acid cocrystal. In some embodiments, Compound 1 is provided as Form C, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form C is substantially similar to the XRPD provided in  FIG.  23   . 
     Methods for preparing Compound 1 Form C are described infra. 
     Compound 1 Form D 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form D. In some embodiments, Compound 1 Form D is a bis-dimethylacetamide (DMA) solvate. In some embodiments, Compound 1 is provided as Form D, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form D is substantially similar to the XRPD provided in  FIG.  25   . 
     Methods for preparing Compound 1 Form D are described infra. 
     Compound 1 Form E 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form E. In some embodiments, Compound 1 Form E is a tris-dimethylsulfoxide (DMSO) solvate. In some embodiments, Compound 1 is provided as Form E, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form E is substantially similar to the XRPD provided in  FIG.  27   . 
     Methods for preparing Compound 1 Form E are described infra. 
     Compound 1 Form F 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form F. In some embodiments, Compound 1 Form F is a bis-N-methyl-2-pyrrolidone (NMP) solvate. In some embodiments, Compound 1 is provided as Form F, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form F is substantially similar to the XRPD provided in  FIG.  29   . 
     Methods for preparing Compound 1 Form F are described infra. 
     Compound 1 Form G 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form G. In some embodiments, Compound 1 Form G is a bis-dimethylformamide (DMF) solvate. In some embodiments, Compound 1 is provided as Form G, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form G is substantially similar to the XRPD provided in  FIG.  31   . 
     Methods for preparing Compound 1 Form G are described infra. 
     Compound 1 Form H 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form H. In some embodiments, Compound 1 is provided as Form H, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form H is substantially similar to the XRPD provided in  FIG.  28   . 
     Methods for preparing Compound 1 Form H are described infra. 
     Compound 1 Form J 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form J. In some embodiments, Compound 1 is provided as Form J, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form J is substantially similar to the XRPD provided in  FIG.  32   . 
     Methods for preparing Compound 1 Form J are described infra. 
     Compound 1 Form K 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form K. In some embodiments, Compound 1 is provided as Form K, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form K is substantially similar to the XRPD provided in  FIG.  33   . 
     Methods for preparing Compound 1 Form K are described infra. 
     Compound 1 Form L 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form L. In some embodiments, Compound 1 Form L is a bis-tetrahydrofuran (THF) solvate. In some embodiments, Compound 1 is provided as Form L, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form L is substantially similar to the XRPD provided in  FIG.  34   . 
     Methods for preparing Compound 1 Form L are described infra. 
     Compound 1 Form M 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form M. In some embodiments, Compound 1 Form M is a bis- or tris-dimethylformamide (DMF) solvate. In some embodiments, Compound 1 is provided as Form M, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form M is substantially similar to the XRPD provided in  FIG.  36   . 
     Methods for preparing Compound 1 Form M are described infra. 
     Compound 1 Form N 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form N. In some embodiments, Compound 1 Form N is anhydrous. In some embodiments, Compound 1 is provided as Form N, substantially free from other free base forms of Compound 1. 
     In some embodiments, Compound 1 Form N has at least 1, 2, 3, 4 or 5 X-ray Powder Diffraction (XRPD) peaks selected from the angles (degrees 2 theta±0.20) listed in Table N-1 
     
       
         
           
               
             
               
                 TABLE N-1 
               
               
                   
               
               
                 XRPD Peak Positions for Compound 1 Form N 
               
               
                 Angle/° 2θ 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 8.08 
               
               
                 8.62 
               
               
                 9.75 
               
               
                 9.81 
               
               
                 11.76 
               
               
                 12.62 
               
               
                 13.44 
               
               
                 13.56 
               
               
                 15.73 
               
               
                 16.21 
               
               
                 17.31 
               
               
                 17.59 
               
               
                 17.87 
               
               
                 19.32 
               
               
                 19.54 
               
               
                 19.74 
               
               
                 20.21 
               
               
                 20.74 
               
               
                 21.00 
               
               
                 21.39 
               
               
                 21.62 
               
               
                 22.15 
               
               
                 22.52 
               
               
                 23.13 
               
               
                 23.86 
               
               
                 24.34 
               
               
                 24.66 
               
               
                 25.02 
               
               
                 25.57 
               
               
                 25.90 
               
               
                 26.38 
               
               
                 27.06 
               
               
                 27.31 
               
               
                 27.85 
               
               
                 28.49 
               
               
                 28.77 
               
               
                 29.55 
               
               
                 29.81 
               
               
                 30.47 
               
               
                 31.04 
               
               
                 31.79 
               
               
                 32.46 
               
               
                 33.27 
               
               
                 34.45 
               
               
                 34.83 
               
               
                   
               
            
           
         
       
     
     In some embodiments, Compound 1 Form N is characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (degrees 2 theta±0.20) and corresponding d-spacing of: 
     
       
         
           
               
             
               
                 TABLE N-2 
               
             
            
               
                   
               
               
                 XRPD Peak Positions and d-Spacing for Compound 1 Form N 
               
            
           
           
               
               
               
            
               
                   
                 Angle/° 2θ 
                 d-spacing/Angstrom 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 8.08 
                 10.933 ± 0.270  
               
               
                   
                 8.62 
                 10.250 ± 0.237  
               
               
                   
                 9.75 
                 9.064 ± 0.185 
               
               
                   
                 9.81 
                 9.009 ± 0.183 
               
               
                   
                 11.76 
                 7.519 ± 0.127 
               
               
                   
                 12.62 
                 7.009 ± 0.111 
               
               
                   
                 13.44 
                 6.583 ± 0.098 
               
               
                   
                 13.56 
                 6.525 ± 0.096 
               
               
                   
                 15.73 
                 5.629 ± 0.071 
               
               
                   
                 16.21 
                 5.464 ± 0.067 
               
               
                   
                 17.31 
                 5.119 ± 0 059 
               
               
                   
                 17.59 
                 5.038 ± 0.057 
               
               
                   
                 17.87 
                 4.960 ± 0.055 
               
               
                   
                 19.32 
                 4.591 ± 0.047 
               
               
                   
                 19.54 
                 4.539 ± 0.046 
               
               
                   
                 19.74 
                 4.494 ± 0.045 
               
               
                   
                 20.21 
                 4.390 ± 0.043 
               
               
                   
                 20.74 
                 4.279 ± 0.041 
               
               
                   
                 21.00 
                 4.227 ± 0.040 
               
               
                   
                 21.39 
                 4.151 ± 0.038 
               
               
                   
                 21.62 
                 4.107 ± 0.038 
               
               
                   
                 22.15 
                 4.010 ± 0.036 
               
               
                   
                 22.52 
                 3.945 ± 0.035 
               
               
                   
                 23.13 
                 3.842 ± 0.033 
               
               
                   
                 23.86 
                 3.726 ± 0.031 
               
               
                   
                 24.34 
                 3.654 ± 0.030 
               
               
                   
                 24.66 
                 3.607 ± 0.029 
               
               
                   
                 25.02 
                 3.556 ± 0.028 
               
               
                   
                 25.57 
                 3.481 ± 0.027 
               
               
                   
                 25.90 
                 3.437 ± 0.026 
               
               
                   
                 26.38 
                 3.376 ± 0.025 
               
               
                   
                 27.06 
                 3.293 ± 0.024 
               
               
                   
                 27.31 
                 3.263 ± 0.023 
               
               
                   
                 27.85 
                 3.201 ± 0.023 
               
               
                   
                 28.49 
                 3.130 ± 0.022 
               
               
                   
                 28.77 
                 3.101 ± 0.021 
               
               
                   
                 29.55 
                 3.020 ± 0.020 
               
               
                   
                 29.81 
                 2.995 ± 0.020 
               
               
                   
                 30.47 
                 2.931 ± 0.019 
               
               
                   
                 31.04 
                 2.879 ± 0.018 
               
               
                   
                 31.79 
                 2.813 ± 0.017 
               
               
                   
                 32.46 
                 2.756 ± 0.017 
               
               
                   
                 33.27 
                 2.691 ± 0.016 
               
               
                   
                 34.45 
                 2.601 ± 0.015 
               
               
                   
                 34.83 
                 2.574 ± 0.014 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, Compound 1 Form N is characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has two or more peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has three or more peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has four or more peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has five or more peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has six or more peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has seven or more peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has eight or more peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta. In some embodiments, Compound 1 Form N is characterized in that it has peaks in its X-ray powder diffraction pattern selected from those at about 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31 degrees 2-theta, corresponding to d-spacing shown in Table N-2 above. As used herein, the term “about”, when used in reference to a degree 2-theta value refers to the stated value±0.2 degree 2-theta. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form N is substantially similar to the XRPD provided in  FIG.  36   . 
     Methods for preparing Compound 1 Form N are described infra. 
     Compound 1 Form O 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form O. In some embodiments, Compound 1 is provided as Form O, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form O is substantially similar to the XRPD provided in  FIG.  14 A  (bottom spectrum). 
     Methods for preparing Compound 1 Form O are described infra. 
     Compound 1 Form P 
     In certain embodiments, the present disclosure provides a solid form of Compound 1 referred to herein as Form P. In some embodiments, Compound 1 Form P is a mono- or bis-ethyl acetate solvate. In some embodiments, Compound 1 is provided as Form P, substantially free from other free base forms of Compound 1. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 1 Form P is substantially similar to the XRPD provided in  FIG.  38   . 
     Methods for preparing Compound 1 Form P are described infra. 
     II. Combinations of Co-Formers with Compound 1 
     In some embodiments, Compound 1 and a co-former (e.g., an acid) are combined to provide a species where Compound 1 and the co-former are, e.g., ionically bonded or are hydrogen bonded to form a provided compound, as described herein. It is contemplated that provided compounds can exist in a variety of physical forms. For example, provided compounds can be in solution, suspension, or in solid form. In certain embodiments, a provided compound is in solid form. When provided compounds are in solid form, said compounds may be amorphous, crystalline, or a mixture thereof. Exemplary solid forms of Compounds 2 through 5 are described in more detail below. 
     2. Compound 2 (Hydrochloric Acid×Compound 1) 
     In some embodiments, the present disclosure provides a chemical species Compound 2 comprising Compound 1 and hydrochloric acid: 
     
       
         
         
             
             
         
       
     
     It is contemplated that Compound 2 can exist in a variety of physical forms. For example, Compound 2 can be in solution, suspension, or in solid form. In certain embodiments, Compound 2 is in solid form. When Compound 2 is in solid form, said compound may be amorphous, crystalline, or a mixture thereof. 
     In some embodiments, a solid form of Compound 2 has a stoichiometry of (Compound 1):(hydrochloric acid) that is about 1:1. As used herein, the term “about”, when used in reference to a stoichiometric ratio refers to 1:(1f0.25) ratio of (Compound 1):(co-former, e.g., an acid), e.g., a 1:(10.25) ratio, a 1:(10.2) ratio, a 1:(1f0.1) ratio, or a 1:(1±0.05) ratio. 
     In some embodiments, the present disclosure provides Compound 2 substantially free of impurities. As used herein, the term “substantially free of impurities” means that the compound contains no significant amount of extraneous matter. Such extraneous matter may include excess hydrochloric acid, excess Compound 1, residual solvents, or any other impurities that may result from the preparation of, and/or isolation of, Compound 2. In certain embodiments, at least about 95% by weight of Compound 2 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of Compound 2 is present. In still other embodiments of the disclosure, at least about 99% by weight of Compound 2 is present. 
     According to one embodiment, Compound 2 is present in an amount of at least about 97.0, 97.5, 98.0, 98.5, 99.0, 99.5, or 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, Compound 2 contains no more than about 3.0 area percent HPLC of total organic impurities and, in certain embodiments, no more than about 1.5 area percent HPLC total organic impurities relative to the total area of the HPLC chromatogram. In some embodiments, Compound 2 contains no more than about 1.0 area percent HPLC of any single impurity; no more than about 0.6 area percent HPLC of any single impurity, and, in certain embodiments, no more than about 0.5 area percent HPLC of any single impurity, relative to the total area of the HPLC chromatogram. 
     The structure depicted for Compound 2 is also meant to include all tautomeric forms of Compound 2. Additionally, structures depicted here are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a  13 C- or  14 C-enriched carbon are within the scope of this disclosure. 
     It has been found that Compound 2 can exist in a variety of solid forms. Exemplary such forms include polymorphs such as those described herein. 
     As used herein, the term “polymorph” refers to the different crystal structures into which a compound, or a salt or co-crystal or solvate thereof, can crystallize. 
     In some embodiments, Compound 2 is amorphous. In some embodiments, Compound 2 is amorphous, and is substantially free of crystalline Compound 2. As used herein, the term “substantially free of crystalline Compound 2” means that the compound contains no significant amount of crystalline Compound 2. In some embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of amorphous Compound 2 is present. In some embodiments, at least about 99% by weight of amorphous Compound 2 is present. 
     In certain embodiments, Compound 2 is a crystalline solid. In other embodiments, Compound 2 is a crystalline solid substantially free of amorphous Compound 2. As used herein, the term “substantially free of amorphous Compound 2” means that the compound contains no significant amount of amorphous Compound 2. In certain embodiments, at least about 95% by weight of crystalline Compound 2 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of crystalline Compound 2 is present. In still other embodiments of the disclosure, at least about 99% by weight of crystalline Compound 2 is present. 
     When Compound 1 is in contact with one equivalent of HCl in various solvents, the resulting Compound 2 can exist in at least two polymorphic forms. In some embodiments, the present disclosure provides a polymorphic form of Compound 2 referred to herein as Form A. In some embodiments, the present disclosure provides a polymorphic form of Compound 2 referred to herein as Form B. 
     Compound 2 Form A 
     In some embodiments, Compound 2 Form A has at least 1, 2, 3, 4 or 5 X-ray Powder Diffraction (XRPD) peaks selected from the angles (degrees 2 theta±0.20) listed in Table 3 below. 
     
       
         
           
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 XRPD Peak Positions for Compound 2 Form A 
               
               
                 Angle/° 2θ 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 7.38 
               
               
                 8.17 
               
               
                 10.01 
               
               
                 11.29 
               
               
                 11.98 
               
               
                 12.3 
               
               
                 12.75 
               
               
                 14.83 
               
               
                 15.63 
               
               
                 16.6 
               
               
                 17.41 
               
               
                 17.59 
               
               
                 18.15 
               
               
                 19.21 
               
               
                 20.12 
               
               
                 20.71 
               
               
                 21.64 
               
               
                 22.11 
               
               
                 22.38 
               
               
                 23.29 
               
               
                 23.60 
               
               
                 23.83 
               
               
                 24.16 
               
               
                 24.54 
               
               
                 24.77 
               
               
                 25.40 
               
               
                 26.24 
               
               
                 27.23 
               
               
                 28.2 
               
               
                 28.61 
               
               
                 29.85 
               
               
                 30.14 
               
               
                 30.40 
               
               
                 30.63 
               
               
                 31.25 
               
               
                 32.05 
               
               
                   
               
            
           
         
       
     
     In some embodiments, Compound 2 Form A is characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (degrees 2 theta±0.20) and corresponding d-spacing of: 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 XRPD Peak Positions and d-Spacing for Compound 2 Form A 
               
            
           
           
               
               
               
            
               
                   
                 Angle/° 2θ 
                 d-spacing/Angstrom 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 7.38 
                 11.969 ± 0.324  
               
               
                   
                 8.17 
                 10.813 ± 0.264  
               
               
                   
                 10.01 
                 8.829 ± 0.176 
               
               
                   
                 11.29 
                 7.831 ± 0.138 
               
               
                   
                 11.98 
                 7.382 ± 0.123 
               
               
                   
                 12.30 
                 7.190 ± 0.116 
               
               
                   
                 12.75 
                 6.937 ± 0.108 
               
               
                   
                 14.83 
                 5.969 ± 0.080 
               
               
                   
                 15.63 
                 5.665 ± 0.072 
               
               
                   
                 16.60 
                 5.336 ± 0.064 
               
               
                   
                 17.41 
                 5.090 ± 0.058 
               
               
                   
                 17.59 
                 5.038 ± 0.057 
               
               
                   
                 18.15 
                 4.884 ± 0.053 
               
               
                   
                 19.21 
                 4.617 ± 0.048 
               
               
                   
                 20.12 
                 4.410 ± 0.043 
               
               
                   
                 20.71 
                 4.285 ± 0.041 
               
               
                   
                 21.64 
                 4.103 ± 0.037 
               
               
                   
                 22.11 
                 4.017 ± 0.036 
               
               
                   
                 22.38 
                 3.969 ± 0.035 
               
               
                   
                 23.29 
                 3.816 ± 0.032 
               
               
                   
                 23.60 
                 3.767 ± 0.031 
               
               
                   
                 23.83 
                 3.731 ± 0.031 
               
               
                   
                 24.16 
                 3.681 ± 0.030 
               
               
                   
                 24.54 
                 3.625 ± 0.029 
               
               
                   
                 24.77 
                 3.591 ± 0.029 
               
               
                   
                 25.40 
                 3.504 ± 0.027 
               
               
                   
                 26.24 
                 3.394 ± 0.025 
               
               
                   
                 27.23 
                 3.272 ± 0.024 
               
               
                   
                 28.20 
                 3.162 ± 0.022 
               
               
                   
                 28.61 
                 3.118 ± 0.021 
               
               
                   
                 29.85 
                 2.991 ± 0.020 
               
               
                   
                 30.14 
                 2.963 ± 0.019 
               
               
                   
                 30.40 
                 2.938 ± 0.019 
               
               
                   
                 30.63 
                 2.916 ± 0.019 
               
               
                   
                 31.25 
                 2.860 ± 0.018 
               
               
                   
                 32.05 
                 2.790 ± 0.017 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, Compound 2 Form A is characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has two or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has three or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has four or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has five or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has six or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has seven or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has eight or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has nine or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has ten or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has eleven or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has twelve or more peaks in its X-ray powder diffraction pattern selected from those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta. In some embodiments, Compound 2 Form A is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23 degrees 2 theta, corresponding to d-spacing shown in Table 4 above. As used herein, the term “about”, when used in reference to a degree 2-theta value refers to the stated value±0.2 degree 2-theta. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 2 Form A is substantially similar to the XRPD provided in  FIG.  4   . 
     Methods for preparing Compound 2 Form A are described infra. 
     3. Compound 3 (Hydrobromic Acid×Compound 1) 
     In some embodiments, the present disclosure provides a chemical species Compound 3 comprising Compound 1 and hydrobromic acid: 
     
       
         
         
             
             
         
       
     
     It is contemplated that Compound 3 can exist in a variety of physical forms. For example, Compound 3 can be in solution, suspension, or in solid form. In certain embodiments, Compound 3 is in solid form. When Compound 3 is in solid form, said compound may be amorphous, crystalline, or a mixture thereof. 
     In one embodiment, a solid form of Compound 3 has a stoichiometry of (Compound 1):(hydrobromic acid) that is about 1:1. 
     In some embodiments, the present disclosure provides Compound 3 substantially free of impurities. As used herein, the term “substantially free of impurities” means that the compound contains no significant amount of extraneous matter. Such extraneous matter may include excess hydrobromic acid, excess Compound 1, residual solvents, or any other impurities that may result from the preparation of, and/or isolation of, Compound 3. In certain embodiments, at least about 95% by weight of Compound 3 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of Compound 3 is present. In still other embodiments of the disclosure, at least about 99% by weight of Compound 3 is present. 
     According to one embodiment, Compound 3 is present in an amount of at least about 97.0, 97.5, 98.0, 98.5, 99.0, 99.5, or 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, Compound 3 contains no more than about 3.0 area percent HPLC of total organic impurities and, in certain embodiments, no more than about 1.5 area percent HPLC total organic impurities relative to the total area of the HPLC chromatogram. In other embodiments, Compound 3 contains no more than about 1.0 area percent HPLC of any single impurity; no more than about 0.6 area percent HPLC of any single impurity, and, in certain embodiments, no more than about 0.5 area percent HPLC of any single impurity, relative to the total area of the HPLC chromatogram. 
     The structure depicted for Compound 3 is also meant to include all tautomeric forms of Compound 3. Additionally, structures depicted here are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a  13 C- or  14 C-enriched carbon are within the scope of this disclosure. 
     In some embodiments, Compound 3 is amorphous. In some embodiments, Compound 3 is amorphous, and is substantially free of crystalline Compound 3. As used herein, the term “substantially free of crystalline Compound 3” means that the compound contains no significant amount of crystalline Compound 3. In some embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of amorphous Compound 3 is present. In some embodiments, at least about 99% by weight of amorphous Compound 3 is present. 
     In certain embodiments, Compound 3 is a crystalline solid. In other embodiments, Compound 3 is a crystalline solid substantially free of amorphous Compound 3. As used herein, the term “substantially free of amorphous Compound 3” means that the compound contains no significant amount of amorphous Compound 3. In certain embodiments, at least about 95% by weight of crystalline Compound 3 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of crystalline Compound 3 is present. In still other embodiments of the disclosure, at least about 99% by weight of crystalline Compound 3 is present. 
     It has been found that Compound 3 can exist in at least one solid form. In some embodiments, the present disclosure provides a solid form of Compound 3 referred to herein as Form A. 
     Compound 3 Form A 
     In some embodiments, Compound 3 Form A has at least 1, 2, 3, 4 or 5 X-ray Powder Diffraction (XRPD) peaks selected from the angles (degrees 2 theta±0.2) listed in Table 5 below. 
     
       
         
           
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 XRPD Peak Positions for Compound 3 Form A 
               
               
                 Angle/° 2θ 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 7.10 
               
               
                 8.72 
               
               
                 9.82 
               
               
                 10.45 
               
               
                 10.68 
               
               
                 12.14 
               
               
                 12.40 
               
               
                 13.33 
               
               
                 13.87 
               
               
                 14.25 
               
               
                 14.53 
               
               
                 15.19 
               
               
                 15.99 
               
               
                 16.38 
               
               
                 17.18 
               
               
                 17.35 
               
               
                 17.51 
               
               
                 18.10 
               
               
                 18.61 
               
               
                 19 27 
               
               
                 19.62 
               
               
                 20.13 
               
               
                 20.42 
               
               
                 20.76 
               
               
                 21.01 
               
               
                 21.48 
               
               
                 22.40 
               
               
                 22.93 
               
               
                 24.43 
               
               
                 24.98 
               
               
                 25.14 
               
               
                 25.95 
               
               
                 26.27 
               
               
                 26.76 
               
               
                 27.23 
               
               
                 27.91 
               
               
                 28.09 
               
               
                 28.57 
               
               
                 28.77 
               
               
                 29.32 
               
               
                 29.86 
               
               
                 30.84 
               
               
                 31.09 
               
               
                   
               
            
           
         
       
     
     In some embodiments, Compound 3 Form A is characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (degrees 2 theta±0.2) and corresponding d-spacing of: 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 XRPD Peak Positions and d-Spacing for Compound 3 Form A 
               
            
           
           
               
               
               
            
               
                   
                 Angle/° 2θ 
                 d-spacing/Angstrom 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 7.10 
                 12.440 ± 0.350  
               
               
                   
                 8.72 
                 10.132 ± 0.232  
               
               
                   
                 9.82 
                 9.000 ± 0.183 
               
               
                   
                 10.45 
                 8.459 ± 0.161 
               
               
                   
                 10.68 
                 8.277 ± 0.155 
               
               
                   
                 12.14 
                 7.285 ± 0.120 
               
               
                   
                 12.40 
                 7.132 ± 0.115 
               
               
                   
                 13.33 
                 6.637 ± 0.099 
               
               
                   
                 13.87 
                 6.380 ± 0.092 
               
               
                   
                 14.25 
                 6.210 ± 0.087 
               
               
                   
                 14.53 
                 6.091 ± 0.083 
               
               
                   
                 15.19 
                 5.828 ± 0.076 
               
               
                   
                 15.99 
                 5.538 ± 0.069 
               
               
                   
                 16.38 
                 5.407 ± 0.066 
               
               
                   
                 17.18 
                 5.157 ± 0.060 
               
               
                   
                 17.35 
                 5.107 ± 0.058 
               
               
                   
                 17.51 
                 5.061 ± 0.057 
               
               
                   
                 18.10 
                 4.897 ± 0.054 
               
               
                   
                 18.61 
                 4.764 ± 0.051 
               
               
                   
                 19.27 
                 4.602 ± 0.047 
               
               
                   
                 19.62 
                 4.521 ± 0.046 
               
               
                   
                 20.13 
                 4.408 ± 0.043 
               
               
                   
                 20.42 
                 4.346 ± 0.042 
               
               
                   
                 20.76 
                 4.275 ± 0.041 
               
               
                   
                 21.01 
                 4.225 ± 0.040 
               
               
                   
                 21.48 
                 4.134 ± 0.038 
               
               
                   
                 22.40 
                 3.966 ± 0.035 
               
               
                   
                 22.93 
                 3.875 ± 0.033 
               
               
                   
                 24.43 
                 3.641 ± 0.029 
               
               
                   
                 24.98 
                 3.562 ± 0.028 
               
               
                   
                 25.14 
                 3.539 ± 0.028 
               
               
                   
                 25.95 
                 3.431 ± 0.026 
               
               
                   
                 26.27 
                 3.389 ± 0.025 
               
               
                   
                 26.76 
                 3.329 ± 0.024 
               
               
                   
                 27.23 
                 3.272 ± 0.024 
               
               
                   
                 27.91 
                 3.194 ± 0.022 
               
               
                   
                 28.09 
                 3.174 ± 0.022 
               
               
                   
                 28.57 
                 3.122 ± 0.021 
               
               
                   
                 28.77 
                 3.100 ± 0.021 
               
               
                   
                 29.32 
                 3.044 ± 0.020 
               
               
                   
                 29.86 
                 2.990 ± 0.020 
               
               
                   
                 30.84 
                 2.897 ± 0.018 
               
               
                   
                 31.09 
                 2.874 ± 0.018 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, Compound 3 Form A is characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has two or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has three or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has four or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has five or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has six or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has seven or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has eight or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has nine or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has ten or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has eleven or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has twelve or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has thirteen or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has fourteen or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has fifteen or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has sixteen or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has seventeen or more peaks in its X-ray powder diffraction pattern selected from those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta. In some embodiments, Compound 3 Form A is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23 degrees 2 theta, corresponding to d-spacing shown in Table 6 above. As used herein, the term “about”, when used in reference to a degree 2-theta value refers to the stated value±0.2 degree 2-theta. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 3 Form A is substantially similar to the XRPD provided in  FIG.  8   . 
     Methods for preparing Compound 3 Form A are described infra. 
     4. Compound 4 (Methanesulfonic Acid×Compound 1) 
     In some embodiments, the present disclosure provides a chemical species Compound 4 comprising Compound 1 and methanesulfonic acid: 
     
       
         
         
             
             
         
       
     
     It is contemplated that Compound 4 can exist in a variety of physical forms. For example, Compound 4 can be in solution, suspension, or in solid form. In certain embodiments, Compound 4 is in solid form. When Compound 4 is in solid form, said compound may be amorphous, crystalline, or a mixture thereof. 
     In some embodiments, a solid form of Compound 4 has a stoichiometry of (Compound 1):(methanesulfonic acid) that is about 1:1. 
     In some embodiments, the present disclosure provides Compound 4 substantially free of impurities. As used herein, the term “substantially free of impurities” means that the compound contains no significant amount of extraneous matter. Such extraneous matter may include excess methanesulfonic acid, excess Compound 1, residual solvents, or any other impurities that may result from the preparation of, and/or isolation of, Compound 4. In certain embodiments, at least about 95% by weight of Compound 4 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of Compound 4 is present. In still other embodiments of the disclosure, at least about 99% by weight of Compound 4 is present. 
     According to one embodiment, Compound 4 is present in an amount of at least about 97.0, 97.5, 98.0, 98.5, 99.0, 99.5, or 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, Compound 4 contains no more than about 3.0 area percent HPLC of total organic impurities and, in certain embodiments, no more than about 1.5 area percent HPLC total organic impurities relative to the total area of the HPLC chromatogram. In other embodiments, Compound 4 contains no more than about 1.0 area percent HPLC of any single impurity; no more than about 0.6 area percent HPLC of any single impurity, and, in certain embodiments, no more than about 0.5 area percent HPLC of any single impurity, relative to the total area of the HPLC chromatogram. 
     The structure depicted for Compound 4 is also meant to include all tautomeric forms of Compound 4. Additionally, structures depicted here are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a  13 C- or  14 C-enriched carbon are within the scope of this disclosure. 
     In some embodiments, Compound 4 is amorphous. In some embodiments, Compound 4 is amorphous, and is substantially free of crystalline Compound 4. As used herein, the term “substantially free of crystalline Compound 4” means that the compound contains no significant amount of crystalline Compound 4. In some embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of amorphous Compound 4 is present. In some embodiments, at least about 99% by weight of amorphous Compound 4 is present. 
     In certain embodiments, Compound 4 is a crystalline solid. In other embodiments, Compound 4 is a crystalline solid substantially free of amorphous Compound 4. As used herein, the term “substantially free of amorphous Compound 4” means that the compound contains no significant amount of amorphous Compound 4. In certain embodiments, at least about 95% by weight of crystalline Compound 4 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of crystalline Compound 4 is present. In still other embodiments of the disclosure, at least about 99% by weight of crystalline Compound 4 is present. 
     It has been found that Compound 4 can exist in at least two polymorphic forms. In some embodiments, the present disclosure provides a polymorphic form of Compound 4 referred to herein as Form A. In some embodiments, the present disclosure provides a polymorphic form of Compound 4 referred to herein as Form B. 
     Compound 4 Form A 
     In some embodiments, Compound 4 Form A has at least 1, 2, 3, 4 or 5 X-ray Powder Diffraction (XRPD) peaks selected from the angles (degrees 2 theta±0.2) listed in Table 7 below. 
     
       
         
           
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 XRPD Peak Positions for Compound 4 Form A 
               
               
                 Angle/° 2θ 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 7.35 
               
               
                 8.52 
               
               
                 9.31 
               
               
                 10.03 
               
               
                 10.65 
               
               
                 11.89 
               
               
                 13.19 
               
               
                 13.68 
               
               
                 14.48 
               
               
                 15.45 
               
               
                 15.89 
               
               
                 16.84 
               
               
                 17.49 
               
               
                 17.66 
               
               
                 18.80 
               
               
                 19.19 
               
               
                 19.48 
               
               
                 20.14 
               
               
                 20.57 
               
               
                 21.43 
               
               
                 21.79 
               
               
                 22.23 
               
               
                 22.52 
               
               
                 22.82 
               
               
                 23.58 
               
               
                 23.94 
               
               
                 24.60 
               
               
                 25.43 
               
               
                 25.83 
               
               
                 26.45 
               
               
                 27.06 
               
               
                 27.62 
               
               
                 28.31 
               
               
                 29.22 
               
               
                 29.83 
               
               
                 30.73 
               
               
                 32.08 
               
               
                   
               
            
           
         
       
     
     In some embodiments, Compound 4 Form A is characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (degrees 2 theta±0.2) and corresponding d-spacing of: 
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 XRPD Peak Positions and d-Spacing for Compound 4 Form A 
               
            
           
           
               
               
               
            
               
                   
                 Angle/° 2θ 
                 d-spacing/Angstrom 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 7.35 
                 12.018 ± 0.327  
               
               
                   
                 8.52 
                 10.370 ± 0.243  
               
               
                   
                 9.31 
                 9.492 ± 0.203 
               
               
                   
                 10.03 
                 8.812 ± 0.175 
               
               
                   
                 10.65 
                 8.300 ± 0.155 
               
               
                   
                 11.89 
                 7.437 ± 0.125 
               
               
                   
                 13.19 
                 6.707 ± 0.101 
               
               
                   
                 13.68 
                 6.468 ± 0.094 
               
               
                   
                 14.48 
                 6.112 ± 0.084 
               
               
                   
                 15.45 
                 5.731 ± 0.074 
               
               
                   
                 15.89 
                 5.573 ± 0.070 
               
               
                   
                 16.84 
                 5.261 ± 0.062 
               
               
                   
                 17.49 
                 5.067 ± 0.057 
               
               
                   
                 17.66 
                 5.018 ± 0.056 
               
               
                   
                 18.80 
                 4.716 ± 0.050 
               
               
                   
                 19.19 
                 4.621 ± 0.048 
               
               
                   
                 19.48 
                 4.553 ± 0.046 
               
               
                   
                 20.14 
                 4.405 ± 0.043 
               
               
                   
                 20.57 
                 4.314 ± 0.041 
               
               
                   
                 21.43 
                 4.143 ± 0.038 
               
               
                   
                 21.79 
                 4.075 ± 0.037 
               
               
                   
                 22.23 
                 3.996 ± 0.035 
               
               
                   
                 22.52 
                 3.945 ± 0.035 
               
               
                   
                 22.82 
                 3.894 ± 0.034 
               
               
                   
                 23.58 
                 3.770 ± 0.032 
               
               
                   
                 23.94 
                 3.714 ± 0.031 
               
               
                   
                 24.60 
                 3.616 ± 0.029 
               
               
                   
                 25.43 
                 3.500 ± 0.027 
               
               
                   
                 25.83 
                 3.446 ± 0.026 
               
               
                   
                 26.45 
                 3.367 ± 0.025 
               
               
                   
                 27.06 
                 3.293 ± 0.024 
               
               
                   
                 27.62 
                 3.227 ± 0.023 
               
               
                   
                 28.31 
                 3.150 ± 0.022 
               
               
                   
                 29 22 
                 3.054 ± 0.020 
               
               
                   
                 29.83 
                 2.993 ± 0.020 
               
               
                   
                 30.73 
                 2.907 ± 0.018 
               
               
                   
                 32.08 
                 2.788 ± 0.017 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, Compound 4 Form A is characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has two or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has three or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has four or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has five or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has six or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has seven or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has eight or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has nine or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has ten or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has eleven or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has twelve or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has thirteen or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has fourteen or more peaks in its X-ray powder diffraction pattern selected from those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta. In some embodiments, Compound 4 Form A is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06 degrees 2 theta, corresponding to d-spacing shown in Table 8 above. As used herein, the term “about”, when used in reference to a degree 2-theta value refers to the stated value±0.2 degree 2-theta. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 4 Form A is substantially similar to the XRPD provided in  FIG.  10   . 
     Methods for preparing Compound 4 Form A are described infra. 
     Compound 4 Form B 
     In some embodiments, Compound 4 Form B has at least 1, 2, 3, 4 or 5 X-ray Powder Diffraction (XRPD) peaks selected from the angles (degrees 2 theta 0.2) listed in Table 9 below. 
     
       
         
           
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 XRPD Peak Positions for Compound 4 Form B 
               
               
                 Angle/° 2θ 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 7.42 
               
               
                 8.53 
               
               
                 9.60 
               
               
                 10.31 
               
               
                 12.16 
               
               
                 13.45 
               
               
                 14.75 
               
               
                 15.39 
               
               
                 15.86 
               
               
                 17.76 
               
               
                 18.27 
               
               
                 18.69 
               
               
                 20.07 
               
               
                 20.74 
               
               
                 21.50 
               
               
                 22.45 
               
               
                 23.78 
               
               
                 24.56 
               
               
                 25.13 
               
               
                 25.84 
               
               
                 27.07 
               
               
                 28.04 
               
               
                 29.13 
               
               
                 29.89 
               
               
                 31.14 
               
               
                 32.08 
               
               
                 33.12 
               
               
                   
               
            
           
         
       
     
     In some embodiments, Compound 4 Form B is characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (degrees 2 theta±0.2) and corresponding d-spacing of: 
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 XRPD Peak Positions and d-Spacing for Compound 4 Form B 
               
            
           
           
               
               
               
            
               
                   
                 Angle/° 2θ 
                 d-spacing/Angstrom 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 7.42 
                 11.904 ± 0.320  
               
               
                   
                 8.53 
                 10.358 ± 0.242  
               
               
                   
                 9.60 
                 9.206 ± 0.191 
               
               
                   
                 10.31 
                 8.573 ± 0.166 
               
               
                   
                 12.16 
                 7.273 ± 0.119 
               
               
                   
                 13.45 
                 6.578 ± 0.097 
               
               
                   
                 14.75 
                 6.001 ± 0.081 
               
               
                   
                 15.39 
                 5.753 ± 0.074 
               
               
                   
                 15.86 
                 5.583 ± 0.070 
               
               
                   
                 17.76 
                 4 990 ± 0.056 
               
               
                   
                 18.27 
                 4.852 ± 0.053 
               
               
                   
                 18.69 
                 4.744 ± 0.050 
               
               
                   
                 20.07 
                 4.421 ± 0.044 
               
               
                   
                 20.74 
                 4.279 ± 0.041 
               
               
                   
                 21.50 
                 4.130 ± 0.038 
               
               
                   
                 22.45 
                 3.957 ± 0.035 
               
               
                   
                 23.78 
                 3.739 ± 0.031 
               
               
                   
                 24.56 
                 3.622 ± 0.029 
               
               
                   
                 25.13 
                 3.541 ± 0.028 
               
               
                   
                 25.84 
                 3.445 ± 0.026 
               
               
                   
                 27.07 
                 3.291 ± 0.024 
               
               
                   
                 28.04 
                 3.180 ± 0.022 
               
               
                   
                 29.13 
                 3.063 ± 0.021 
               
               
                   
                 29.89 
                 2.987 ± 0.020 
               
               
                   
                 31.14 
                 2.870 ± 0.018 
               
               
                   
                 32.08 
                 2.788 ± 0.017 
               
               
                   
                 33.12 
                 2.703 ± 0.016 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, Compound 4 Form B is characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has two or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has three or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has four or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has five or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In same embodiments, Compound 4 Form B is characterized in that it has six or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In same embodiments, Compound 4 Form B is characterized in that it has seven or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has eight or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has nine or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has ten or more peaks in its X-ray powder diffraction pattern selected from those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta. In some embodiments, Compound 4 Form B is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07 degrees 2 theta, corresponding to d-spacing shown in Table 10 above. As used herein, the term “about”, when used in reference to a degree 2-theta value refers to the stated value±0.2 degree 2-theta. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 4 Form B is substantially similar to the XRPD provided in  FIG.  12   . 
     Methods for preparing Compound 4 Form B are described infra. 
     5. Compound 5 ((1R)-(−)-10-camphorsulfonic Acid×Compound 1) 
     In some embodiments, the present disclosure provides a chemical species Compound 5 comprising Compound 1 and (1R)-(−)-10-camphorsulfonic acid: 
     
       
         
         
             
             
         
       
     
     It is contemplated that Compound 5 can exist in a variety of physical forms. For example, Compound 5 can be in solution, suspension, or in solid form. In certain embodiments, Compound 5 is in solid form. When Compound 5 is in solid form, said compound may be amorphous, crystalline, or a mixture thereof. 
     In some embodiments, the solid form of Compound 5 has a stoichiometry of (Compound 1):((1R)-(−)-10-camphorsulfonic acid) that is about 1:1. 
     In some embodiments, the present disclosure provides Compound 5 substantially free of impurities. As used herein, the term “substantially free of impurities” means that the compound contains no significant amount of extraneous matter. Such extraneous matter may include excess (1R)-(−)-10-camphorsulfonic acid, excess Compound 1, residual solvents, or any other impurities that may result from the preparation of, and/or isolation of, Compound 5. In certain embodiments, at least about 95% by weight of Compound 5 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of Compound 5 is present. In still other embodiments of the disclosure, at least about 99% by weight of Compound 5 is present. 
     According to one embodiment, Compound 5 is present in an amount of at least about 97.0, 97.5, 98.0, 98.5, 99.0, 99.5, or 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, Compound 5 contains no more than about 3.0 area percent HPLC of total organic impurities and, in certain embodiments, no more than about 1.5 area percent HPLC total organic impurities relative to the total area of the HPLC chromatogram. In other embodiments, Compound 5 contains no more than about 1.0 area percent HPLC of any single impurity; no more than about 0.6 area percent HPLC of any single impurity, and, in certain embodiments, no more than about 0.5 area percent HPLC of any single impurity, relative to the total area of the HPLC chromatogram. 
     The structure depicted for Compound 5 is also meant to include all tautomeric forms of Compound 5. Additionally, structures depicted here are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a  13 C- or  14 C-enriched carbon are within the scope of this disclosure. 
     In some embodiments, Compound 5 is amorphous. In some embodiments, Compound 5 is amorphous, and is substantially free of crystalline Compound 5. As used herein, the term “substantially free of crystalline Compound 5” means that the compound contains no significant amount of crystalline Compound 5. In some embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of amorphous Compound 5 is present. In some embodiments, at least about 99% by weight of amorphous Compound 5 is present. 
     In certain embodiments, Compound 5 is a crystalline solid. In other embodiments, Compound 5 is a crystalline solid substantially free of amorphous Compound 5. As used herein, the term “substantially free of amorphous Compound 5” means that the compound contains no significant amount of amorphous Compound 5. In certain embodiments, at least about 95% by weight of crystalline Compound 5 is present. In certain embodiments, at least about 95%, about 96%, about 97%, about 98%, or about 99% by weight of crystalline Compound 5 is present. In still other embodiments of the disclosure, at least about 99% by weight of crystalline Compound 5 is present. 
     It has been found that Compound 5 can exist in at least one polymorphic form. In some embodiments, the present disclosure provides a polymorphic form of Compound 5 referred to herein as Form C. 
     Compound 5 Form C 
     In some embodiments, Compound 5 Form C has at least 1, 2, 3, 4 or 5 X-ray Powder Diffraction (XRPD) peaks selected from the angles (degrees 2 theta±0.2) listed in Table 11 below. 
     
       
         
           
               
             
               
                 TABLE 11 
               
               
                   
               
               
                 XRPD Peak Positions for Compound 5 Form C 
               
               
                 Angle /°2θ 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 6.55 
               
               
                 9.01 
               
               
                 9.87 
               
               
                 10.49 
               
               
                 11.01 
               
               
                 11.57 
               
               
                 12.05 
               
               
                 12.19 
               
               
                 12.65 
               
               
                 13.14 
               
               
                 13.45 
               
               
                 14.08 
               
               
                 14.30 
               
               
                 14.59 
               
               
                 14.98 
               
               
                 15.39 
               
               
                 16.22 
               
               
                 16.46 
               
               
                 16.94 
               
               
                 17.42 
               
               
                 17.62 
               
               
                 17.74 
               
               
                 18.10 
               
               
                 18.75 
               
               
                 19.36 
               
               
                 19.76 
               
               
                 19.95 
               
               
                 20.16 
               
               
                 20.50 
               
               
                 20.81 
               
               
                 20.91 
               
               
                 21.10 
               
               
                 21.57 
               
               
                 21.99 
               
               
                 22.16 
               
               
                 22.45 
               
               
                 22.87 
               
               
                 23.59 
               
               
                 24.39 
               
               
                 24.66 
               
               
                 25.47 
               
               
                 25.95 
               
               
                 26.48 
               
               
                 26.70 
               
               
                 27.04 
               
               
                 27.30 
               
               
                 27.70 
               
               
                 28.08 
               
               
                   
               
            
           
         
       
     
     In some embodiments, Compound 5 Form C is characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (degrees 2 theta±0.2) and corresponding d-spacing of: 
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 XRPD Peak Positions and d-Spacing for Compound 5 Form C 
               
            
           
           
               
               
               
            
               
                   
                 Angle /°2θ 
                 d-spacing/Angstrom 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 6.55 
                 13.484 ± 0.411  
               
               
                   
                 9.01 
                 9.807 ± 0.217 
               
               
                   
                 9.87 
                 8.954 ± 0.181 
               
               
                   
                 10.49 
                 8.426 ± 0.160 
               
               
                   
                 11.01 
                 8.030 ± 0.145 
               
               
                   
                 11.57 
                 7.642 ± 0.132 
               
               
                   
                 12.05 
                 7.339 ± 0.121 
               
               
                   
                 12.19 
                 7.255 ± 0.119 
               
               
                   
                 12.65 
                 6.992 ± 0.110 
               
               
                   
                 13.14 
                 6.732 ± 0.102 
               
               
                   
                 13.45 
                 6.578 ± 0.097 
               
               
                   
                 14.08 
                 6.285 ± 0.089 
               
               
                   
                 14.30 
                 6.189 ± 0.086 
               
               
                   
                 14.59 
                 6.066 ± 0.083 
               
               
                   
                 14.98 
                 5.909 ± 0.078 
               
               
                   
                 15.39 
                 5.753 ± 0.074 
               
               
                   
                 16.22 
                 5.460 ± 0.067 
               
               
                   
                 16.46 
                 5.381 ± 0.065 
               
               
                   
                 16.94 
                 5.230 ± 0.061 
               
               
                   
                 17.42 
                 5.087 ± 0.058 
               
               
                   
                 17.62 
                 5.029 ± 0.057 
               
               
                   
                 17.74 
                 4.996 ± 0.056 
               
               
                   
                 18.10 
                 4.897 ± 0.054 
               
               
                   
                 18.75 
                 4.729 ± 0.050 
               
               
                   
                 19.36 
                 4.581 ± 0.047 
               
               
                   
                 19.76 
                 4.489 ± 0.045 
               
               
                   
                 19.95 
                 4.447 ± 0.044 
               
               
                   
                 20.16 
                 4.401 ± 0.043 
               
               
                   
                 20.50 
                 4.329 ± 0.042 
               
               
                   
                 20.81 
                 4.265 ± 0.041 
               
               
                   
                 20.91 
                 4.245 ± 0.040 
               
               
                   
                 21.10 
                 4.207 ± 0.039 
               
               
                   
                 21.57 
                 4.116 ± 0.038 
               
               
                   
                 21.99 
                 4.039 ± 0.036 
               
               
                   
                 22.16 
                 4.008 ± 0.036 
               
               
                   
                 22.45 
                 3.957 ± 0.035 
               
               
                   
                 22.87 
                 3.885 ± 0.034 
               
               
                   
                 23.59 
                 3.768 ± 0.031 
               
               
                   
                 24.39 
                 3.647 ± 0.029 
               
               
                   
                 24.66 
                 3.607 ± 0.029 
               
               
                   
                 25.47 
                 3.494 ± 0.027 
               
               
                   
                 25.95 
                 3.431 ± 0.026 
               
               
                   
                 26.48 
                 3.363 ± 0.025 
               
               
                   
                 26.70 
                 3.336 ± 0.025 
               
               
                   
                 27.04 
                 3.295 ± 0.024 
               
               
                   
                 27.30 
                 3.264 ± 0.023 
               
               
                   
                 27.70 
                 3.218 ± 0.023 
               
               
                   
                 28.08 
                 3.176 ± 0.022 
               
               
                   
                 28.41 
                 3.140 ± 0.022 
               
               
                   
                 28.65 
                 3.113 ± 0.021 
               
               
                   
                 29.06 
                 3.071 ± 0.021 
               
               
                   
                 29 30 
                 3.046 ± 0.020 
               
               
                   
                 29.74 
                 3.001 ± 0.020 
               
               
                   
                 30.26 
                 2.951 ± 0.019 
               
               
                   
                 31.41 
                 2.846 ± 0.018 
               
               
                   
                 32.07 
                 2.789 ± 0.017 
               
               
                   
                   
               
            
           
         
       
     
     In some embodiments, Compound 5 Form C is characterized in that it has one or more peaks in its X-ray powder diffraction pattern selected from those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta. In some embodiments, Compound 5 Form C is characterized in that it has two or more peaks in its X-ray powder diffraction pattern selected from those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta. In some embodiments, Compound 5 Form C is characterized in that it has three or more peaks in its X-ray powder diffraction pattern selected from those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta. In some embodiments, Compound 5 Form C is characterized in that it has four or more peaks in its X-ray powder diffraction pattern selected from those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta. In some embodiments, Compound 5 Form C is characterized in that it has five or more peaks in its X-ray powder diffraction pattern selected from those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta. In some embodiments, Compound 5 Form C is characterized in that it has six or more peaks in its X-ray powder diffraction pattern selected from those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta. In some embodiments, Compound 5 Form C is characterized in that it has seven or more peaks in its X-ray powder diffraction pattern selected from those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta. In some embodiments, Compound 5 Form C is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta. In some embodiments, Compound 5 Form C is characterized in that it has peaks in its X-ray powder diffraction pattern comprising those at about 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47 degrees 2 theta, corresponding to d-spacing shown in Table 12 above. As used herein, the term “about”, when used in reference to a degree 2-theta value refers to the stated value±0.2 degree 2-theta. 
     In certain embodiments, the X-ray powder diffraction pattern of Compound 5 Form C is substantially similar to the XRPD provided in  FIG.  13   . 
     Methods for preparing Compound 5 Form C are described infra. 
     General Methods of Providing the Compounds 
     Compound 1 is prepared according to the methods described in Example 1. 
     Acid addition compounds of general formula of Compound A, which formula encompasses, inter alia, Compounds 2 through 5, and/or particular forms thereof, are prepared from Compound 1, according to the general Scheme below. 
     
       
         
         
             
             
         
       
     
     In this scheme, “Acid” represents, e.g., any of the co-formers described herein. For instance, each of Compounds 2 through 5, and forms thereof, are prepared from Compound 1 by combining Compound 1 with an appropriate acid under suitable conditions to form the product Compound A. Thus, another aspect of the present disclosure provides a method for preparing Compounds 2 through 5, and forms thereof, by combining Compound 1 with an appropriate acid to form the product Compound A. 
     As described generally above, in some embodiments, the present disclosure provides a method for preparing Compound A: 
     
       
         
         
             
             
         
       
     
     comprising steps of: 
     combining Compound 1: 
     
       
         
         
             
             
         
       
     
     with a suitable co-former (e.g., a suitable acid) and optionally a suitable solvent under conditions suitable for forming Compound A. In some embodiments, the present disclosure provides a solid form of Compound 1 obtained by a process comprising the step of contacting Compound 1 with a suitable acid under conditions and for a time effective to form a solid form (e.g., salt or co-crystal) of Compound 1. 
     In some embodiments, Compound 1 is treated with a co-former selected from: benzenesulfonic acid, camphorsulfonic acid (e.g., (1R)-(−)-10-camphorsulfonic acid), 1,2-ethanedisulfonic acid, ethansulfonic acid, hydrobromic acid, hydrochloric acid, methanesulfonic acid, phosphoric acid, and sulfuric acid. 
     In some embodiments, a suitable co-former is benzenesulfonic acid. 
     In some embodiments, a suitable co-former is (1R)-(−)-10-camphorsulfonic acid. 
     In some embodiments, a suitable co-former is 1,2-ethanedisulfonic acid. 
     In some embodiments, a suitable co-former is ethansulfonic acid. 
     In some embodiments, a suitable co-former is hydrobromic acid. 
     In some embodiments, a suitable co-former is hydrochloric acid. 
     In some embodiments, a suitable co-former is methanesulfonic acid. 
     In some embodiments, a suitable co-former is phosphoric acid. 
     In some embodiments, a suitable co-former is sulfuric acid. 
     A suitable solvent may be any solvent system (e.g., one solvent or a mixture of solvents) in which Compound 1 and/or an acid are soluble, or are at least partially soluble. 
     Examples of suitable solvents useful in the present disclosure include, but are not limited to protic solvents, aprotic solvents, polar aprotic solvent, or mixtures thereof. In certain embodiments, suitable solvents include an ether, an ester, an alcohol, a ketone, or a mixture thereof. In some embodiments, a solvent is one or more organic alcohols. In some embodiments, a solvent is chlorinated. In some embodiments, a solvent is an aromatic solvent. 
     In certain embodiments, a suitable solvent is tetrahydrofuran (THF), 2,2,2-trifluoroethanol, or acetone wherein said solvent is anhydrous or in combination with water. In some embodiments, a suitable solvent is 80:20 acetone/water. In some embodiments, a suitable solvent is THF. In some embodiments, a suitable solvent is 2,2,2-trifluoroethanol. In some embodiments, a suitable solvent is a combination of said solvents. 
     In some embodiments, a suitable solvent is acetic acid, cyclopentyl methyl ether (CPME), dimethylacetamide (DMA), dimethylformamide (DMF), dimethylsulfoxide (DMSO), ethyl acetate, hexafluoroisopropanol (HFIPA), isopropanol (IPA), isopropyl ether (IPE), methyl tert-butyl ether (MTBE), N-methyl-2-pyrrolidone (NMP), tert-amyl methyl ether (TAME), tetrahydrofuran (THF), or 2,2,2-trifluoroethanol (TFE), wherein said solvent is anhydrous or in combination with water. In some embodiments, a suitable solvent is acetic acid. In some embodiments, a suitable solvent is CPME. In some embodiments, a suitable solvent is DMA. In some embodiments, a suitable solvent is DMF. In some embodiments, a suitable solvent is DMSO. In some embodiments, a suitable solvent is ethyl acetate. In some embodiments, a suitable solvent is HFIPA. In some embodiments, a suitable solvent is IPA. In some embodiments, a suitable solvent is IPE. In some embodiments, a suitable solvent is MTBE. In some embodiments, a suitable solvent is NMP. In some embodiments, a suitable solvent is TAME. In some embodiments, a suitable solvent is THF. In some embodiments, a suitable solvent is 80:20 THF/water. In some embodiments, a suitable solvent is 99:1 THF/water. In some embodiments, a suitable solvent is 97:3 THF/water. In some embodiments, a suitable solvent is 93:7 THF/water. In some embodiments, a suitable solvent is TFE. In some embodiments, a suitable solvent is a combination of said solvents. 
     In some embodiments, the present disclosure provides a method for preparing (i) a free base form of Compound 1 or (ii) Compound A, comprising one or more steps of removing a solvent and adding a solvent. In some embodiments, an added solvent is the same as the solvent removed. In some embodiments, an added solvent is different from a solvent removed. Means of solvent removal are known in the synthetic and chemical arts and include, but are not limited to, any of those described herein and in the Exemplification. 
     In some embodiments, a method for preparing (i) a free base form of Compound 1 or (ii) Compound A comprises one or more steps of heating or cooling a preparation. 
     In some embodiments, a method for preparing (i) a free base form of Compound 1 or (ii) Compound A comprises one or more steps of agitating or stirring a preparation. 
     In some embodiments, a method for preparing (i) a free base form of Compound 1 or (ii) Compound A comprises a step of adding a suitable co-former to a solution or slurry of Compound 1. 
     In some embodiments, a method for preparing (i) a free base form of Compound 1 or (ii) Compound A comprises a step of adding a suitable acid to a solution or slurry of Compound 1. 
     In some embodiments, a method for preparing (i) a free base form of Compound 1 or (ii) Compound A comprises a step of heating. 
     In certain embodiments, a free base form of Compound 1 or Compound A precipitates from the mixture. In another embodiment, a free base form of Compound 1 or Compound A crystallizes from the mixture. In other embodiments, a free base form of Compound 1 or Compound A crystallizes from solution following seeding of the solution (i.e., adding crystals of a free base form of Compound 1 or Compound A to the solution). 
     A free base form of Compound 1 or Compound A can precipitate out of the reaction mixture, or be generated by removal of part or all of the solvent through methods such as evaporation, distillation, filtration (e.g., nanofiltration, ultrafiltration), reverse osmosis, absorption and reaction, by adding a suitable anti-solvent, by cooling or by different combinations of these methods. 
     As described generally above, a free base form of Compound 1 or Compound A is optionally isolated. It will be appreciated that a free base form of Compound 1 or Compound A may be isolated by any suitable physical means known to one of ordinary skill in the art. In certain embodiments, precipitated solid free base form of Compound 1 or Compound A is separated from the supernatant by filtration. In other embodiments, precipitated solid free base form of Compound 1 or Compound A is separated from the supernatant by decanting the supernatant. 
     In certain embodiments, a free base form of Compound 1 or Compound A is separated from the supernatant by filtration. 
     In certain embodiments, an isolated free base form of Compound 1 or Compound A is dried in air. In other embodiments isolated free base form of Compound 1 or Compound A is dried under reduced pressure, optionally at elevated temperature (e.g., a vacuum oven). 
     Methods of Use 
     The present disclosure provides uses for compounds and compositions described herein. In some embodiments, provided compounds and compositions are useful in medicine (e.g., as therapy). In some embodiments, provided compounds and compositions are useful in research as, for example, analytical tools and/or control compounds in biological assays. 
     In some embodiments, the present disclosure provides methods of administering provided compounds or compositions to a subject in need thereof. In some embodiments, the present disclosure provides methods of administering provided compounds or compositions to a subject suffering from or susceptible to a disease, disorder, or condition associated with JAK2. 
     In some embodiments, provided compounds are useful as JAK2 inhibitors. In some embodiments, provided compounds are useful as Type II JAK2 inhibitors. In some embodiments, the present disclosure provides methods of inhibiting JAK2 in a subject comprising administering a provided compound or composition. In some embodiments, the present disclosure provides methods of inhibiting JAK2 in a biological sample comprising contacting the sample with a provided compound or composition. 
     JAK (e.g., JAK2) has been implicated in various diseases, disorders, and conditions, such as myeloproliferative neoplasms (Vainchenker, W. et al., F1000Research 2018, 7 (F1000 Faculty Rev): 82), atopic dermatitis (Rodrigues, M. A. and Torres, T. J. Derm. Treat. 2019, 31(1), 33-40) and acute respiratory syndrome, hyperinflammation, and/or cytokine storm syndrome ( The Lancet . doi:10.1016/S0140-6736(20)30628-0). Accordingly, in some embodiments, the present disclosure provides methods of treating a disease, disorder or condition associated with JAK2 in a subject in need thereof comprising administering to the subject a provided compound or composition. In some embodiments, a disease, disorder or condition is associated with overexpression of JAK2. 
     In some embodiments, the present disclosure provides methods of treating cancer, comprising administering a provided compound or composition to a subject in need thereof. In some embodiments, the present disclosure provides methods of treating proliferative diseases, comprising administering a provided compound or composition to a subject in need thereof. 
     In some embodiments, the present disclosure provides methods of treating a hematological malignancy, comprising administering a provided compound or composition to a subject in need thereof. In some embodiments, a hematological malignancy is leukemia (e.g., chronic lymphocytic leukemia, acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute monocytic leukemia). In some embodiments, a hematological malignancy is lymphoma (e.g., Burkitt&#39;s lymphoma, Hodgkin&#39;s lymphoma, or non-Hodgkin&#39;s lymphoma). In some embodiments, a non-Hodgkin&#39;s lymphoma is a B-cell lymphoma. In some embodiments, a non-Hodgkin&#39;s lymphoma is a NK/T-cell lymphoma (e.g., cutaneous T-cell lymphoma). In some embodiments, a hematological malignancy is myeloma (e.g., multiple myeloma). In some embodiments, a hematological malignancy is myeloproliferative neoplasm (e.g., polycythemia vera, essential thrombocytopenia, or myelofibrosis). In some embodiments, a hematological malignancy is myelodysplastic syndrome. 
     In some embodiments, the present disclosure provides methods of treating an inflammatory disease, disorder, or condition (e.g., acute respiratory syndrome, hyperinflammation, and/or cytokine storm syndrome (including those associated with COVID-19) or atopic dermatitis), comprising administering a provided compound or composition to a subject in need thereof. 
     In some embodiments, a provided compound or composition is administered as part of a combination therapy. As used herein, the term “combination therapy” refers to those situations in which a subject is simultaneously exposed to two or more therapeutic or prophylactic regimens (e.g., two or more therapeutic or prophylactic agents). In some embodiments, the two or more regimens may be administered simultaneously; in some embodiments, such regimens may be administered sequentially (e.g., all “doses” of a first regimen are administered prior to administration of any doses of a second regimen); in some embodiments, such agents are administered in overlapping dosing regimens. In some embodiments, “administration” of combination therapy may involve administration of one or more agent(s) or modality(ies) to a subject receiving the other agent(s) or modality(ies) in the combination. For clarity, combination therapy does not require that individual agents be administered together in a single composition (or even necessarily at the same time), although in some embodiments, two or more agents, or active moieties thereof, may be administered together in a combination composition. 
     For example, in some embodiments, a provided compound or composition is administered to a subject who is receiving or has received one or more additional therapies (e.g., an anti-cancer therapy and/or therapy to address one or more side effects of such anti-cancer therapy, or otherwise to provide palliative care). Exemplary additional therapies include BCL2 inhibitors (e.g., venetoclax), HDAC inhibitors (e.g., vorinostat), BET inhibitors (e.g., mivebresib), proteasome inhibitors (e.g., bortezomib), LSD1 inhibitors (e.g., IMG-7289), and CXCR2 inhibitors. Useful combinations of a JAK2 inhibitor with BCL2, HDAC, BET, and proteasome inhibitors have been demonstrated in cells derived from cutaneous T-cell lymphoma patients (Yumeen, S., et al., Blood Adv. 2020, 4(10), 2213-2226). A combination of a JAK2 inhibitor with a LSD1 inhibitor demonstrated good efficacy in a mouse model of myeloproliferative neoplasms (Jutzi, J. S., et al., HemaSphere 2018, 2(3), http://dx.doi.org/10.1097/HS9.00000000000054). CXCR2 activity has been shown to modulate signaling pathways involved in tumor growth, angiogenesis, and/or metastasis, including the JAK-STAT3 pathway (Jaffer, T., Ma, D. Transl. Cancer Res. 2016, 5 (Suppl. 4), S616-S628). 
     Pharmaceutical Compositions 
     In another aspect, the present disclosure provides pharmaceutical compositions comprising any of the compounds described herein (e.g., any of Compounds 1-5) or any of the compounds described herein (e.g., any of Compounds 1-5) in combination with a pharmaceutically acceptable excipient (e.g., carrier). In some embodiments, the present disclosure provides a pharmaceutical composition for oral administration, comprising a solid form of any of Compounds 1-5. 
     The pharmaceutical compositions include optical isomers, diastereomers, or pharmaceutically acceptable salts of the compounds disclosed herein. 
     A “pharmaceutically acceptable carrier,” as used herein refers to pharmaceutical excipients, for example, pharmaceutically, physiologically, acceptable organic or inorganic carrier substances suitable for enteral or parenteral application that do not deleteriously react with the active agent. Suitable pharmaceutically acceptable carriers include water and one or more fillers, disintegrants, lubricants, glidants, anti-adherents, and/or anti-statics, etc. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and/or aromatic substances and the like that do not deleteriously react with the compounds of the disclosure. 
     Provided pharmaceutical compositions can be in a variety of forms including oral dosage forms, topical creams, topical patches, iontophoresis forms, suppository, nasal spray and/or inhaler, eye drops, intraocular injection forms, depot forms, as well as injectable and infusible solutions. Methods of preparing pharmaceutical compositions are well known in the art. 
     In some embodiments, provided compounds are formulated in a unit dosage form for ease of administration and uniformity of dosage. The expression “unit dosage form” as used herein refers to a physically discrete unit of an active agent (e.g., a compound described herein) for administration to a subject. Typically, each such unit contains a predetermined quantity of active agent. In some embodiments, a unit dosage form contains an entire single dose of the agent. In some embodiments, more than one unit dosage form is administered to achieve a total single dose. In some embodiments, administration of multiple unit dosage forms is required, or expected to be required, in order to achieve an intended effect. A unit dosage form may be, for example, a liquid pharmaceutical composition containing a predetermined quantity of one or more active agents, a solid pharmaceutical composition (e.g., a tablet, a capsule, or the like) containing a predetermined amount of one or more active agents, a sustained release formulation containing a predetermined quantity of one or more active agents, or a drug delivery device containing a predetermined amount of one or more active agents, etc. 
     Provided compositions may be administered using any amount and any route of administration effective for treating or lessening the severity of any disease or disorder described herein. 
     EXEMPLARY EMBODIMENTS 
     The following numbered embodiments, while non-limiting, are exemplary of certain aspects of the present disclosure: 
     1. A solid form of Compound 1: 
     
       
         
         
             
             
         
       
     
     or a salt or co-crystal form thereof.
 
2. The solid form of embodiment 1, wherein the solid form is selected from the group consisting of a Compound 1 salt or co-crystal form of benzenesulfonic acid, camphorsulfonic acid (e.g., (1R)-(−)-10-camphorsulfonic acid), 1,2-ethanedisulfonic acid, ethansulfonic acid, hydrobromic acid, hydrochloric acid, methanesulfonic acid, phosphoric acid, and sulfuric acid.
 
3. The solid form of embodiment 1 or 2, wherein the solid form is a Compound 1 salt of hydrochloric acid.
 
4. The solid form of any one of the preceding embodiments, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide hydrochloride.
 
5. The solid form of any one of the preceding embodiments, wherein the solid form is Compound 2 comprising Compound 1 and hydrochloric acid:
 
     
       
         
         
             
             
         
       
     
     6. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has three or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
7. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has four or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
8. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has five or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
9. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has six or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
10. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has seven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
11. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has eight or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
12. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has nine or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
13. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has ten or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
14. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has eleven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
15. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has twelve or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
16. The solid form of any one of the preceding embodiments, where the solid form is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of 7.38, 8.17, 11.98, 12.30, 15.63, 19.21, 20.12, 20.71, 21.64, 22.11, 24.16, 25.40, and 27.23.
 
17. The solid form of any one of the preceding embodiments, where the solid form is Compound 2 Form A and is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of;
 
                             Angle/°2θ                                    7.38       8.17       10.01       11.29       11.98       12.3       12.75       14.83       15.63       16.6       17.41       17.59       18.15       19.21       20.12       20.71       21.64       22.11       22.38       23.29       23.60       23.83       24.16       24.54       24.77       25.40       26.24       27 23       28.2       28.61       29.85       30.14       30.40       30.63       31.25       32.05                    
18. The solid form of any one of embodiments 6-17, wherein the XRPD pattern is collected using Cu Kα radiation with a wavelength of 1.54059 Å, optionally wherein the XRPD pattern is collected according to the parameters in Table 13.
 
19. The solid form of any one of the preceding embodiments, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 278.8° C.
 
20. The solid form of any one of the preceding embodiments, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 0.3% between 42-165° C.
 
21. The solid form of any one of the preceding embodiments, characterized by an about 0.95% mass increase between 5 and 95% RH by dynamic vapor sorption (DVS) analysis.
 
22. The solid form of embodiment 1 or 2, wherein the solid form is a Compound 1 salt of hydrobromic acid.
 
23. The solid form of any one of embodiments 1, 2, or 22, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide hydrobromide.
 
24. The solid form of any one of embodiments 1, 2, or 22-23, wherein the solid form is Compound 3 comprising Compound 1 and hydrobromic acid:
 
     
       
         
         
             
             
         
       
     
     25. The solid form of any one of embodiments 1, 2, or 22-24, where the solid form is characterized in that it has three or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
26. The solid form of any one of embodiments 1, 2, or 22-25, where the solid form is characterized in that it has four or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
27. The solid form of any one of embodiments 1, 2, or 22-26, where the solid form is characterized in that it has five or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
28. The solid form of any one of embodiments 1, 2, or 22-27, where the solid form is characterized in that it has six or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
29. The solid form of any one of embodiments 1, 2, or 22-28, where the solid form is characterized in that it has seven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
30. The solid form of any one of embodiments 1, 2, or 22-29, where the solid form is characterized in that it has eight or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
31. The solid form of any one of embodiments 1, 2, or 22-30, where the solid form is characterized in that it has nine or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
32. The solid form of any one of embodiments 1, 2, or 22-31, where the solid form is characterized in that it has ten or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
33. The solid form of any one of embodiments 1, 2, or 22-32, where the solid form is characterized in that it has eleven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
34. The solid form of any one of embodiments 1, 2, or 22-33, where the solid form is characterized in that it has twelve or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
35. The solid form of any one of embodiments 1, 2, or 22-34, where the solid form is characterized in that it has thirteen or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
36. The solid form of any one of embodiments 1, 2, or 22-35, where the solid form is characterized in that it has fourteen or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
37. The solid form of any one of the embodiments 1, 2, or 22-36, where the solid form is characterized in that it has fifteen or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
38. The solid form of any one of embodiments 1, 2, or 22-37, where the solid form is characterized in that it has sixteen or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
39. The solid form of any one of embodiments 1, 2, or 22-38, where the solid form is characterized in that it has seventeen or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
40. The solid form of any one of embodiments 1, 2, or 22-39, where the solid form is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of 8.72, 10.68, 12.14, 13.87, 14.53, 15.99, 16.38, 19.62, 20.13, 20.42, 20.76, 21.01, 22.93, 24.43, 24.98, 25.14, 26.76, and 27.23.
 
41. The solid form of any one of embodiments 1, 2, or 22-40, where the solid form is Compound 3 Form A and is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of.
 
                             Angle/°2θ                                    7.10       8.72       9.82       10.45       10.68       12.14       12.40       13.33       13.87       14.25       14.53       15.19       15.99       16.38       17.18       17.35       17.51       18.10       18.61       19.27       19.62       20.13       20.42       20.76       21.01       21.48       22.40       22.93       24.43       24.98       25.14       25.95       26.27       26.76       27.23       27.91       28.09       28.57       28.77       29 32       29.86       30.84       31.09                    
42. The solid form of any one of embodiments 25-41, wherein the XRPD pattern is collected using Cu Kα radiation with a wavelength of 1.54059 Å, optionally wherein the XRPD pattern is collected according to the parameters in Table 13.
 
43. The solid form of any one of embodiments 1, 2, or 22-42, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 281.6° C.
 
44. The solid form of any one of embodiments 1, 2, or 22-43, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 3.4% between 61-150° C.
 
45. The solid form of embodiment 1 or 2, wherein the solid form is a Compound 1 salt of methanesulfonic acid.
 
46. The solid form of any one of embodiments 1, 2, or 45, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-h]pyridin-6-yl)oxy)pyridin-2-yl)acetamide mesylate.
 
47. The solid form of any one of embodiments 1, 2, or 45-46, wherein the solid form is Compound 4 comprising Compound 1 and methanesulfonic acid:
 
     
       
         
         
             
             
         
       
     
     48. The solid form of any one of embodiments 1, 2, or 45-47, where the solid form is characterized in that it has three or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
49. The solid form of any one of embodiments 1, 2, or 45-48, where the solid form is characterized in that it has four or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
50. The solid form of any one of embodiments 1, 2, or 45-49, where the solid form is characterized in that it has five or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
51. The solid form of any one of embodiments 1, 2, or 45-50, where the solid form is characterized in that it has six or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
52. The solid form of any one of embodiments 1, 2, or 45-51, where the solid form is characterized in that it has seven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
53. The solid form of any one of embodiments 1, 2, or 45-52, where the solid form is characterized in that it has eight or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
54. The solid form of any one of embodiments 1, 2, or 45-53, where the solid form is characterized in that it has nine or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
55. The solid form of any one of embodiments 1, 2, or 45-54, where the solid form is characterized in that it has ten or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
56. The solid form of any one of embodiments 1, 2, or 45-55, where the solid form is characterized in that it has eleven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
57. The solid form of any one of embodiments 1, 2, or 45-56, where the solid form is characterized in that it has twelve or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
58. The solid form of any one of embodiments 1, 2, or 45-57, where the solid form is characterized in that it has thirteen or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
59. The solid form of any one of embodiments 1, 2, or 45-58, where the solid form is characterized in that it has fourteen or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
60. The solid form of any one of embodiments 1, 2, or 45-59, where the solid form is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of 8.52, 9.31, 11.89, 14.48, 15.45, 15.89, 18.80, 19.19, 20.14, 20.57, 23.94, 24.60, 25.83, 26.45, and 27.06.
 
61. The solid form of any one of embodiments 1, 2, or 45-60, where the solid form is Compound 4 Form A and is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of:
 
                             Angle/°2θ                                    7.35       8.52       9.31       10.03       10.65       11.89       13.19       13.68       14.48       15.45       15.89       16.84       17.49       17.66       18.80       19.19       19.48       20.14       20.57       21.43       21.79       22 23       99 50       22.82       23.58       23.94       24.60       25.43       25.83       26.45       27.06       27.62       28.31       29.22       29.83       30.73       32.08                    
62. The solid form of any one of embodiments 48-61, wherein the XRPD pattern is collected using Cu Kα radiation with a wavelength of 1.54059 Å, optionally wherein the XRPD pattern is collected according to the parameters in Table 13.
 
63. The solid form of any one of embodiments 1, 2, or 45-62, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 295.5° C.
 
64. The solid form of any one of embodiments 1, 2, or 45-63, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 3.3% between 44-114° C.
 
65. The solid form of any one of embodiments 1, 2, or 45-47, where the solid form is characterized in that it has three or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
66. The solid form of any one of embodiments 1, 2, 45-47, or 65 where the solid form is characterized in that it has four or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
67. The solid form of any one of embodiments 1, 2, 45-47, or 65-66 where the solid form is characterized in that it has five or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
68. The solid form of any one of embodiments 1, 2, 45-47, or 65-66 where the solid form is characterized in that it has six or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
69. The solid form of any one of embodiments 1, 2, 45-47, or 65-68 where the solid form is characterized in that it has seven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
70. The solid form of any one of embodiments 1, 2, 45-47, or 65-69 where the solid form is characterized in that it has eight or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
71. The solid form of any one of embodiments 1, 2, 45-47, or 65-70 where the solid form is characterized in that it has nine or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
72. The solid form of any one of embodiments 1, 2, 45-47, or 65-71 where the solid form is characterized in that it has ten or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
73. The solid form of any one of embodiments 1, 2, 45-47, or 65-72 where the solid form is characterized in that it has more peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of 8.53, 9.60, 10.31, 12.16, 14.75, 15.86, 20.07, 20.74, 22.45, 24.56, and 27.07.
 
74. The solid form of any one of embodiments 1, 2, 45-47, or 65-73 where the solid form is Compound 4 Form B and is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of:
 
                             Angle/°2θ                                    7.42       8.53       9.60       10.31       12.16       13.45       14.75       15.39       15.86       17.76       18.27       18.69       20.07       20.74       21.50       22.45       23.78       24.56       25.13       25.84       27.07       28.04       29.13       29.89       31.14       32.08       33.12                    
75. The solid form of any one of embodiments 65-74, wherein the XRPD pattern is collected using Cu Kα radiation with a wavelength of 1.5405929 Å, optionally wherein the XRPD pattern is collected according to the parameters in Table 13.
 
76. The solid form of any one of embodiments 1 or 2, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide camsylate.
 
77. The solid form of embodiment 1, 2, or 76 wherein the solid form is a Compound 1 salt of (1R)-(−)-10-camphorsulfonic acid.
 
78. The solid form of any one of embodiments 1, 2, or 76-77, wherein the solid form is Compound 5 comprising Compound 1 and (1R)-(−)-10-camphorsulfonic acid.
 
     
       
         
         
             
             
         
       
     
     79. The solid form of any one of embodiments 1, 2, or 76-78, where the solid form is characterized in that it has three or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47.
 
80. The solid form of any one of embodiments 1, 2, or 76-79, where the solid form is characterized in that it has four or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47.
 
81. The solid form of any one of embodiments 1, 2, or 76-80, where the solid form is characterized in that it has five or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47.
 
82. The solid form of any one of embodiments 1, 2, or 76-81, where the solid form is characterized in that it has six or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47.
 
83. The solid form of any one of embodiments 1, 2, or 76-82, where the solid form is characterized in that it has seven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47.
 
84. The solid form of any one of embodiments 1, 2, or 76-83, where the solid form is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of 6.55, 9.01, 12.05, 12.65, 14.08, 22.16, 22.45, and 25.47.
 
85. The solid form of any one of embodiments 1, 2, or 76-84, where the solid form is Compound 5 Form C and is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of:
 
                             Angle/°2θ                                    6.55       9.01       9.87       10.49       11.01       11.57       12.05       12.19       12.65       13.14       13.45       14.08       14.30       14.59       14.98       15.39       16.22       16.46       16.94       17.42       17.62       17.74       18.10       18.75       19.36       19.76       19.95       20.16       20.50       20.81       20.91       21.10       21.57       21.99       22.16       22.45       22.87       23.59       24.39       24.66       25.47       25.95       26.48       26.70       27.04       27.30       27.70       28.08                    
86. The solid form of any one of embodiments 79-85, wherein the XRPD pattern is collected using Cu Kα radiation with a wavelength of 1.5405929 Å, optionally wherein the XRPD pattern is collected according to the parameters in Table 13.
 
87. The solid form of embodiment 1, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide.
 
88. The solid form of any one of embodiments 1 or 87, where the solid form is characterized in that it has three or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
89. The solid form of any one of embodiments 1 or 87-88, where the solid form is characterized in that it has four or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
90. The solid form of any one of embodiments 1 or 87-89, where the solid form is characterized in that it has five or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
91. The solid form of any one of embodiments 1 or 87-90, where the solid form is characterized in that it has six or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
92. The solid form of any one of embodiments 1 or 87-91, where the solid form is characterized in that it has seven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
93. The solid form of any one of embodiments 1 or 87-92, where the solid form is characterized in that it has eight or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
94. The solid form of any one of embodiments 1 or 87-93, where the solid form is characterized in that it has nine or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
95. The solid form of any one of embodiments 1 or 87-94, where the solid form is characterized in that it has ten or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
96. The solid form of any one of embodiments 1 or 87-95, where the solid form is characterized in that it has eleven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
97. The solid form of any one of embodiments 1 or 87-96, where the solid form is characterized in that it has twelve or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
98. The solid form of any one of embodiments 1 or 87-97, where the solid form is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of 7.33, 11.22, 11.46, 14.01, 16.89, 18.94, 19.70, 21.71, 23.31, 23.56, 25.22, 26.20, and 26.58.
 
99. The solid form of any one of embodiments 88-98, wherein the XRPD pattern is collected using Cu Kα radiation with a wavelength of 1.5405929 Å, optionally wherein the XRPD pattern is collected according to the parameters in Table 13.
 
100. The solid form of any one of embodiments 1 or 87-99, characterized by an about 4.8% mass increase between 5 and 95% RH by dynamic vapor sorption (DVS) analysis.
 
101. The solid form of embodiment 1, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide besylate.
 
102. The solid form of embodiment 1, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide edisylate.
 
103. The solid form of embodiment 1, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide esylate.
 
104. The solid form of embodiment 1, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide phosphate.
 
105. The solid form of embodiment 1, wherein the solid form is N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide sulfate.
 
106. A solid form of Compound 1:
 
     
       
         
         
             
             
         
       
     
     prepared by the method of Example 1.
 
107. A solid form of Compound 2;
 
     
       
         
         
             
             
         
       
     
     prepared by a method comprising the steps of adding hydrochloric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form of Compound 2.
 
108. A solid form of Compound 2:
 
     
       
         
         
             
             
         
       
     
     prepared by a method comprising the steps of adding hydrochloric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form of Compound 2.
 
109. A solid form of Compound 3:
 
     
       
         
         
             
             
         
       
     
     prepared by a method comprising the steps of adding hydrobromic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form of Compound 3.
 
110. A solid form of Compound 3:
 
     
       
         
         
             
             
         
       
     
     prepared by a method comprising the steps of adding hydrobromic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form of Compound 3.
 
111. A solid form of Compound 4:
 
     
       
         
         
             
             
         
       
     
     prepared by a method comprising the steps of adding methanesulfonic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form of Compound 4.
 
112. A solid form of Compound 4:
 
     
       
         
         
             
             
         
       
     
     prepared by a method comprising the steps of adding methanesulfonic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, removing the solvent, and drying in a vacuum oven at 45° C. to provide the solid form of Compound 4.
 
113. A solid form of Compound 5:
 
     
       
         
         
             
             
         
       
     
     prepared by a method comprising the steps of adding a solution of (1R)-(−)-10-camphorsulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, isolating the solids, and drying in a vacuum oven at ambient temperature to provide the solid form of Compound 5.
 
114. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide besylate, prepared by a method comprising the steps of adding a solution of benzenesulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, and then removing the solvent to provide the solid form.
 
115. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide besylate, prepared by a method comprising the steps of adding a solution of benzenesulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, removing the solvent, and drying in a vacuum oven at ambient temperature to provide the solid form.
 
116. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide besylate, prepared by a method comprising the steps of adding a solution of benzenesulfonic acid in 2,2,2-trifluoroethanol to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form.
 
117. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide edisylate, prepared by a method comprising the steps of adding a solution of 1,2-ethanedisulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, and then removing the solvent to provide the solid form.
 
118. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide edisylate, prepared by a method comprising the steps of adding a solution of 1,2-ethanedisulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, removing the solvent, and drying in a vacuum oven at ambient temperature to provide the solid form.
 
119. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide edisylate, prepared by a method comprising the steps of adding a slurry of 1,2-ethanedisulfonic acid in 2,2,2-trifluoroethanol to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form.
 
120. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide esylate, prepared by a method comprising the steps of adding ethanesulfonic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form.
 
121. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide esylate, prepared by a method comprising the steps of adding ethanesulfonic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form.
 
122. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide phosphate, prepared by a method comprising the steps of adding phosphoric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form.
 
123. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide phosphate, prepared by a method comprising the steps of adding phosphoric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, and then removing the solvent to provide the solid form.
 
124. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide sulfate, prepared by a method comprising the steps of adding sulfuric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form.
 
125. A solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide sulfate, prepared by a method comprising the steps of adding sulfuric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyidin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, and then removing the solvent to provide the solid form.
 
126. The solid form according to any one of embodiments 1-125, wherein the solid form of the compound has a ratio of about 1:1 of Compound 1 to co-former.
 
127. The solid form according to any one of embodiments 1-126, wherein said solid form is crystalline.
 
128. The solid form according to any one of embodiments 1-127, wherein said solid form is substantially free of the amorphous form of the compound.
 
129. The solid form according to any one of embodiments 1-126, wherein said solid form is amorphous.
 
130. The solid form according to any one of embodiments 1-129, wherein said solid form is substantially free of impurities.
 
131. A pharmaceutical composition comprising the solid form according to any one of embodiments 1-130 and a pharmaceutical acceptable carrier or excipient.
 
132. A process for preparing a solid form of Compound 2:
 
     
       
         
         
             
             
         
       
     
     the process comprising the steps of adding hydrochloric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form of Compound 2.
 
133. A process for preparing a solid form of Compound 2;
 
     
       
         
         
             
             
         
       
     
     the process comprising the steps of adding hydrochloric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form of Compound 2.
 
134. A process for preparing a solid form of Compound 3:
 
     
       
         
         
             
             
         
       
     
     the process comprising the steps of adding hydrobromic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form of Compound 3.
 
135. A process for preparing a solid form of Compound 3:
 
     
       
         
         
             
             
         
       
     
     the process comprising the steps of adding hydrobromic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form of Compound 3.
 
136. A process for preparing a solid form of Compound 4:
 
     
       
         
         
             
             
         
       
     
     the process comprising the steps of adding methanesulfonic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form of Compound 4.
 
137. A process for preparing a solid form of Compound 4:
 
     
       
         
         
             
             
         
       
     
     the process comprising the steps of adding methanesulfonic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, removing the solvent, and drying in a vacuum oven at 45° C. to provide the solid form of Compound 4.
 
138. A process for preparing a solid form of Compound 5:
 
     
       
         
         
             
             
         
       
     
     the process comprising the steps of adding a solution of (1R)-(−)-10-camphorsulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, isolating the solids, and drying in a vacuum oven at ambient temperature to provide the solid form of Compound 5.
 
139. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide besylate, the process comprising the steps of adding a solution of benzenesulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, and then removing the solvent to provide the solid form.
 
140. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide besylate, the process comprising the steps of adding a solution of benzenesulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, removing the solvent, and drying in a vacuum oven at ambient temperature to provide the solid form.
 
141. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide besylate, the process comprising the steps of adding a solution of benzenesulfonic acid in 2,2,2-trifluoroethanol to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form.
 
142. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide edisylate, the process comprising the steps of adding a solution of 1,2-ethanedisulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, and then removing the solvent to provide the solid form.
 
143. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide edisylate, the process comprising the steps of adding a solution of 1,2-ethanedisulfonic acid in tetrahydrofuran to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, removing the solvent, and drying in a vacuum oven at ambient temperature to provide the solid form.
 
144. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide edisylate, the process comprising the steps of adding a slurry of 1,2-ethanedisulfonic acid in 2,2,2-trifluoroethanol to N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form.
 
145. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide esylate, the process comprising the steps of adding ethanesulfonic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form.
 
146. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide esylate, the process comprising the steps of adding ethanesulfonic acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, cooling the resulting solution to −20° C., and then removing the solvent to provide the solid form.
 
147. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide phosphate, the process comprising the steps of adding phosphoric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form.
 
148. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide phosphate, the process comprising the steps of adding phosphoric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, and then removing the solvent to provide the solid form.
 
149. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide sulfate, the process comprising the steps of adding sulfuric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-11H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in tetrahydrofuran, and then removing the solvent to provide the solid form.
 
150. A process for preparing a solid form of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide sulfate, the process comprising the steps of adding sulfuric acid to a slurry of N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-11-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide in 2,2,2-trifluoroethanol, and then removing the solvent to provide the solid form.
 
151. A method of inhibiting JAK2 in a subject comprising administering the compound of any one of embodiments 1-130 or the composition of embodiment 131.
 
152. A method of treating a disease, disorder, or condition associated with JAK2, comprising administering to a subject in need thereof the compound of any one of embodiments 1-130 or the composition of embodiment 131.
 
153. A method of treating cancer, comprising administering to a subject in need thereof the compound of any one of embodiments 1-130 or the composition of embodiment 131.
 
154. A method of treating a hematological malignancy, comprising administering to a subject in need thereof the compound of any one of embodiments 1-130 or the composition of embodiment 131.
 
155. The method of embodiment 154, wherein the hematological malignancy is leukemia or lymphoma.
 
156. A method of treating a myeloproliferative neoplasm, comprising administering to a subject in need thereof the compound of any one of embodiments 1-130 or the composition of embodiment 131.
 
157. The method of embodiment 156, wherein the myeloproliferative neoplasm is polycythemia vera, essential thrombocytopenia or myelofibrosis.
 
158. A solid form of Compound 1:
 
     
       
         
         
             
             
         
       
     
     159. The solid form of embodiment 158, wherein the solid form is a hydrate.
 
160. The solid form of embodiment 158 or 159, wherein the solid form is characterized in that it has three or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60.
 
161. The solid form of embodiment 158 or 159, wherein the solid form is characterized in that it has four or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60.
 
162. The solid form of embodiment 158 or 159, wherein the solid form is characterized in that it has five or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60.
 
163. The solid form of embodiment 158 or 159, wherein the solid form is characterized in that it has six or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60.
 
164. The solid form of embodiment 158 or 159, wherein the solid form is characterized in that it has seven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60.
 
165. The solid form of embodiment 158 or 159, wherein the solid form is characterized in that it has eight or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60.
 
166. The solid form of embodiment 158 or 159, wherein the solid form is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 7.32, 11.15, 13.99, 16.58, 18.95, 21.68, 23.56, 25.23, and 26.60.
 
167. The solid form of any of embodiments 158-166, wherein the solid form is Compound 1 Form A and is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of:
 
                             Angle/°2θ                                    7.32       9.57       9.77       11.15       11.45       12.90       13.20       13.99       14.41       14.69       16.39       16.58       16.85       17.24       17.98       18.60       18.95       19.23       19.68       20.23       20.75       21.29       21.68       22.19       22.40       22.93       23.56       23.98       24.51       25.23       25.97       26.60       27.25       27.80       28.78       29.07       29.78       30.70                    
168. The solid form of any one of embodiments 160-167, wherein the XRPD pattern is collected using Cu Kα radiation with a wavelength of 1.54059 Å, optionally wherein the XRPD pattern is collected according to the parameters in Table 13.
 
169. The solid form of any one of embodiments 158-168, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 117.9° C. and/or about 307.8° C.
 
170. The solid form of any one of embodiments 158-169, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 9.3% between 41-136° C.
 
171. The solid form of embodiment 158, wherein the solid form is anhydrous.
 
172. The solid form of embodiment 158 or 171, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  22   .
 
173. The solid form of any one of embodiments 158, 171, and 172, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 307.8° C.
 
174. The solid form of any one of embodiments 158 and 171-173, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 0.1% between 50-121° C. and/or a weight loss of about 0.2% between 229-267° C.
 
175. The solid form of embodiment 158, wherein the solid form is an acetic acid solvate.
 
176. The solid form of embodiment 158 or 175, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  23   .
 
177. The solid form of any one of embodiments 158, 175, and 176, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 102.8° C. and/or about 190.1° C. and/or about 308.4° C.
 
178. The solid form of any one of embodiments 158 and 175-177, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 16.6% between 71-137° C. and/or a weight loss of about 8% between 171-203° C.
 
179. The solid form of embodiment 158, wherein the solid form is a dimethylacetamide solvate.
 
180. The solid form of embodiment 158 or 179, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  25   .
 
181. The solid form of any one of embodiments 158, 179, and 180, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 117.7° C. and/or about 305.4° C.
 
182. The solid form of any one of embodiments 158 and 179-181, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 25.5% between 101-186° C.
 
183. The solid form of embodiment 158, wherein the solid form is a dimethylsulfoxide solvate.
 
184. The solid form of embodiment 158 or 183, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  27   .
 
185. The solid form of embodiment 158, wherein the solid form is a N-methyl-2-pyrrolidone solvate.
 
186. The solid form of embodiment 158 or 185, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  29   .
 
187. The solid form of any one of embodiments 158, 185, and 186, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 126.5° C. and/or about 305.4° C.
 
188. The solid form of any one of embodiments 158 and 185-187, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 27.5% between 104-233° C.
 
189. The solid form of embodiment 158, wherein the solid form is a dimethylformamide solvate.
 
190. The solid form of embodiment 158 or 189, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  31   .
 
191. The solid form of embodiment 158, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  28   .
 
192. The solid form of embodiment 158, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  32   .
 
193. The solid form of embodiment 158, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  33   .
 
194. The solid form of embodiment 158, wherein the solid form is a tetrahydrofuran solvate.
 
195. The solid form of embodiment 158 or 194, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  34   .
 
196. The solid form of embodiment 158 or 194, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  35   .
 
197. The solid form of embodiment 158 or 171, wherein the solid form is characterized in that it has three or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta 0.2) of 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31.
 
198. The solid form of embodiment 158 or 171, wherein the solid form is characterized in that it has four or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31.
 
199. The solid form of embodiment 158 or 171, wherein the solid form is characterized in that it has five or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31.
 
200. The solid form of embodiment 158 or 171, wherein the solid form is characterized in that it has six or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta 0.2) of 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31.
 
201. The solid form of embodiment 158 or 171, wherein the solid form is characterized in that it has seven or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31.
 
202. The solid form of embodiment 158 or 171, wherein the solid form is characterized in that it has eight or more peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31.
 
203. The solid form of embodiment 158 or 171, wherein the solid form is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern selected from those at angles (degrees 2 theta±0.2) of 8.08, 11.76, 15.73, 17.31, 19.32, 19.54, 23.13, 25.90, and 27.31.
 
204. The solid form of any one of embodiments 158 and 197-203, wherein the solid form is Compound 1 Form N and is characterized in that it has peaks in its X-ray powder diffraction (XRPD) pattern comprising those at angles (degrees 2 theta±0.2) of:
 
                             Angle/°2θ                                    8.08       8.62       9.75       9.81       11.76       12.62       13.44       13.56       15.73       16.21       17.31       17.59       17.87       19.32       19.54       19.74       20.21       20.74       21.00       21.39       21.62       22.15       22.52       23.13       23.86       24.34       24.66       25.02       25.57       25.90       26.38       27.06       27.31       27.85       28.49       28.77       29.55       29.81       30.47       31.04       31.79       32.46       33.27       34.45       34.83                    
205. The solid form of any one of embodiments 197-204, wherein the XRPD pattern is collected using Cu Kα radiation with a wavelength of 1.5405929 Å, optionally wherein the XRPD pattern is collected according to the parameters in Table 13.
 
206. The solid form of any one of embodiments 158 and 197-205, characterized by a differential scanning calorimetry (DSC) endotherm having a minima at about 307.2° C.
 
207. The solid form of any one of embodiments 158 and 197-206, characterized by a thermogravimetric analysis (TGA) with a weight loss of about 0.1% between 50-120° C. and/or a weight loss of about 0.2% between 209-252° C.
 
208. The solid form of embodiment 158, wherein the solid form is an ethyl acetate solvate.
 
209. The solid form of embodiment 158 or 208, wherein the solid form is characterized in that it has a X-ray powder diffraction pattern substantially similar to  FIG.  38   .
 
210. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 2 in water, and then removing the solvent to provide the solid form of Compound 1.
 
211. The solid form of embodiment 210, wherein the method further comprises steps of adding hydrochloric acid to a slurry of Compound 1 in tetrahydrofuran, and then removing the solvent to provide the Compound 2.
 
212. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in tert-amyl methyl ether, and then removing the solvent to provide the solid form of Compound 1.
 
213. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in acetic acid, and then removing the solvent to provide the solid form of Compound 1.
 
214. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in dimethylacetamide, and then removing the solvent to provide the solid form of Compound 1.
 
215. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in dimethylsulfoxide, and then removing the solvent to provide the solid form of Compound 1.
 
216. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in N-methyl-2-pyrrolidone, and then removing the solvent to provide the solid form of Compound 1.
 
217. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in dimethylformamide, and then removing the solvent to provide the solid form of Compound 1.
 
218. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in dimethylsulfoxide, removing the solvent, and drying the resulting solids in an oven to provide the solid form of Compound 1.
 
219. A solid form of Compound 1 prepared by a method comprising steps of providing a solution of Compound 1 in hexafluoroisopropanol, and then removing the solvent to provide the solid form of Compound 1.
 
220. A solid form of Compound 1 prepared by a method comprising steps of providing a solution of Compound 1 in 2,2,2-trifluoroethanol, and then removing the solvent to provide the solid form of Compound 1.
 
221. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in 99:1 tetrahydrofuran:water, and then removing the solvent to provide the solid form of Compound 1.
 
222. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in 97:3 tetrahydrofuran:water, and then removing the solvent to provide the solid form of Compound 1.
 
223. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in cyclopentyl methyl ether, and then removing the solvent to provide the solid form of Compound 1.
 
224. A solid form of Compound 1 prepared by a method comprising steps of stirring Compound 1 in ethyl acetate, and then removing the solvent to provide the solid form of Compound 1.
 
225. The solid form of any one of embodiments 158-224, wherein the solid form is crystalline.
 
226. The solid form of any one of embodiments 158-225, wherein the solid form is substantially free of an amorphous form of Compound 1.
 
227. The solid form of any one of embodiments 158-226, wherein the solid form is substantially free of impurities.
 
228. The solid form of any one of embodiments 158-227, wherein the solid form is substantially free of other free base solid forms of Compound 1.
 
229. The solid form of any one of embodiments 159-170, wherein the solid form is substantially free of Compound 1 Form B.
 
230. A pharmaceutical composition comprising the solid form of any one of embodiments 158-229 and a pharmaceutically acceptable carrier or excipient.
 
231. A process for preparing a solid form of Compound 1, wherein the process comprises steps of stirring Compound 2 in water, and then removing the solvent to provide the solid form of Compound 1.
 
232. The process of embodiment 231, wherein the process further comprises steps of adding hydrochloric acid to a slurry of Compound 1 in tetrahydrofuran, and then removing the solvent to provide Compound 2.
 
233. A process for preparing a solid form of Compound 1, wherein the process comprises steps of stirring Compound 1 in a suitable solvent, and then removing the solvent to provide the solid form of Compound 1.
 
234. The process of embodiment 233, wherein the suitable solvent is tert-amyl methyl ether.
 
235. The process of embodiment 233, wherein the suitable solvent is acetic acid.
 
236. The process of embodiment 233, wherein the suitable solvent is dimethylacetamide.
 
237. The process of embodiment 233, wherein the suitable solvent is dimethylsulfoxide.
 
238. The process of embodiment 233, wherein the suitable solvent is N-methyl-2-pyrrolidone.
 
239. The process of embodiment 233, wherein the suitable solvent is dimethylformamide.
 
240. The process of embodiment 237, wherein the process further comprises a step of drying the resulting solids in an oven to provide the solid form of Compound 1.
 
241. The process of embodiment 233, wherein the suitable solvent is 99:1 tetrahydrofuran:water.
 
242. The process of embodiment 233, wherein the suitable solvent is 97:3 tetrahydrofuran:water.
 
243. The process of embodiment 233, wherein the suitable solvent is cyclopentyl methyl ether.
 
244. The process of embodiment 233, wherein the suitable solvent is ethyl acetate.
 
245. A process for preparing a solid form of Compound 1, wherein the process comprises steps of providing a solution of Compound 1 in a suitable solvent, and then removing the solvent to provide the solid form of Compound 1.
 
246. The process of embodiment 245, wherein the suitable solvent is hexafluoroisopropanol.
 
247. The process of embodiment 245, wherein the suitable solvent is 2,2,2-trifluoroethanol.
 
248. A method of inhibiting JAK2 in a subject comprising administering the compound of any one of embodiments 158-229 or the composition of embodiment 230.
 
249. A method of treating a disease, disorder, or condition associated with JAK2, comprising administering to a subject in need thereof the compound of any one of embodiments 158-229 or the composition of embodiment 230.
 
250. A method of treating cancer, comprising administering to a subject in need thereof the compound of any one of embodiments 158-229 or the composition of embodiment 230.
 
251. A method of treating a hematological malignancy, comprising administering to a subject in need thereof the compound of any one of embodiments 158-229 or the composition of embodiment 230.
 
252. The method of embodiment 251, wherein the hematological malignancy is leukemia or lymphoma.
 
253. A method of treating a myeloproliferative neoplasm, comprising administering to a subject in need thereof the compound of any one of embodiments 158-229 or the composition of embodiment 230.
 
254. The method of embodiment 253, wherein the myeloproliferative neoplasm is polycythemia vera, essential thrombocytopenia or myelofibrosis.
 
     EXAMPLES 
     The examples below are meant to illustrate certain embodiments of the disclosure, and not to limit the scope of the disclosure. 
     General Experimental 
     Abbreviations 
     
         
         ACN Acetonitrile 
         API Active pharmaceutical ingredient 
         B/E Birefringence and extinction 
         BR Birefringence 
         CPME Cyclopentylmethyl ether 
         DCM Dichloromethane 
         DMA Dimethylacetamide 
         DMF Dimethylformamide 
         DMSO Dimethylsulfoxide 
         DSC Differential scanning calorimetry 
         DVS Dynamic (water) vapor sorption 
         Endo/endo Endotherm or endothermic 
         Exo/exo Exotherm or exothermic 
         FB Free base 
         FE Fast evaporation 
         FF Free form 
         HFIPA Hexafluoroisopropanol 
         IPA Isopropyl alcohol 
         IPE Isopropyl ether 
         IS Insufficient solids/sample 
         LIMS Laboratory Information Management System 
         Max/max Maximum or maxima 
         MeOH Methanol 
         MTBE Methyl tert-butyl ether 
         NMP N-methyl-2-pyrrolidone 
         NMR Nuclear magnetic resonance spectroscopy 
         Obs Observation 
         PO Preferred orientation 
         ppt Precipitate or precipitation 
         RH Relative humidity 
         RT Room temperature 
         Soln/soln Solution 
         TAME Tert-amyl methyl ether 
         TFE 2,2,2-trifluoroethanol 
         TG/TGA Thermogravimetry/Thermogravimetric analysis 
         THF Tetrahydrofuran 
         vac Vacuum 
         VRH-XRPD Variable relative humidity X-ray powder diffraction 
         XRF X-ray fluorescence 
         XRPD X-ray powder diffraction 
       
    
     Instruments and Methods 
     A. X-Ray Powder Diffraction (XRPD) 
     Transmission 
     XRPD pattern was collected with a PANalytical X&#39;Pert PRO MPD or PANalytical Empyrean diffractometer using an incident beam of Cu radiation produced using a long, fine-focus source. An elliptically graded multilayer mirror was used to focus Cu Kα X-rays through the specimen and onto the detector. Prior to the analysis, a silicon specimen (NIST SRM 640f) was analyzed to verify the observed position of the Si 111 peak is consistent with the NIST-certified position. A specimen of the sample was sandwiched between 3-μm-thick films and analyzed in transmission geometry. A beam-stop, short antiscatter extension, and antiscatter knife edge were used to minimize the background generated by air. Soller slits for the incident and diffracted beams were used to minimize broadening and asymmetry from axial divergence. Diffraction patterns were collected using a scanning position-sensitive detector (X&#39;Celerator) located 240 mm from the specimen and Data Collector software v. 5.5. 
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 13 
               
               
                   
               
               
                   
                   
                   
                   
                   
                 Collection 
               
               
                 Compound 
                 X-ray wavelength 
                 Scan range 
                 Step size 
                 Speed 
                 time 
               
               
                   
               
             
            
               
                 Compound 1 
                 Cu (1.5405929 Å) 
                 1.0000-40.0041° 2θ 
                 0.0167° 2θ 
                 3.2°/min. 
                 723 s 
               
               
                 Form 1 a   
                   
                   
                   
                   
                   
               
               
                 Compound 5 
                 Cu (1.5405929 Å) 
                 1.0000-40.0041° 2θ 
                 0.0167° 2θ 
                 3.2°/min. 
                 721 s 
               
               
                 Form C a   
                   
                   
                   
                   
                   
               
               
                 Compound 3 
                 Cu (1.54059 Å) 
                 1.00-39.99° 2θ 
                 0.017° 2θ 
                 3.3°/min 
                 718 s 
               
               
                 Form A b   
                   
                   
                   
                   
                   
               
               
                 Compound 2 
                 Cu (1.54059 Å) 
                 1.00-3999° 2θ 
                 0.017° 2θ 
                 3.3°/min. 
                 718 s 
               
               
                 Form A b   
                   
                   
                   
                   
                   
               
               
                 Compound 4 
                 Cu (1.54059 Å) 
                 1.00-39.99° 2θ 
                 0.017° 2θ 
                 3.2°/min. 
                 720 s 
               
               
                 Form A b   
                   
                   
                   
                   
                   
               
               
                 Compound 4 
                 Cu (15405929 Å) 
                 1.0000-40.0041° 2θ 
                 0.0167° 2θ 
                 3.3°/min 
                 719 s 
               
               
                 Form B a   
                   
                   
                   
                   
                   
               
               
                 Compound 1 
                 Cu (1.54059 Å) 
                 1.00-39.99° 2θ 
                 0.017° 2θ 
                 3.2°/min. 
                 724 s 
               
               
                 Form A b   
                   
                   
                   
                   
                   
               
               
                 Compound 1 
                 Cu (1.5405929 Å) 
                 1.0000-40.0041° 2θ 
                 0.0167° 2θ 
                 3.2°/min 
                 722 s 
               
               
                 Form N a   
               
               
                   
               
               
                   a A PANalytical Empyrean X-ray Powder Diffractometer was used. 
               
               
                   b A PANalytical X&#39;Pert PRO MPD X-ray Powder Diffractometer was used. 
               
            
           
         
       
     
     B. Thermogravimetric (TGA) and Differential Scanning Calorimetry (DSC) 
     TG analysis was performed using a Mettler-Toledo TGA/DSC3+ analyzer. Temperature and enthalpy adjustments were performed using indium, tin, and zinc, and then verified with indium. The balance was verified with calcium oxalate. The sample was placed in an open aluminum pan. The pan was then inserted into the TG furnace. A weighed aluminum pan configured as the sample pan was placed on the reference platform. The furnace was heated under nitrogen. The sample was analyzed from 25° C. to 350° C. at 10° C./min. 
     DSC was performed using a Mettler-Toledo DSC3+ differential scanning calorimeter. A tau lag adjustment was performed with indium, tin, and zinc. The temperature and enthalpy were adjusted with octane, phenyl salicylate, indium, tin and zinc. The adjustment was then verified with octane, phenyl salicylate, indium, tin, and zinc. The sample was placed into a hermetically sealed aluminum DSC pan, the weight was accurately recorded, the lid was pierced, and the sample was inserted into the DSC cell. A weighed aluminum pan configured as the sample pan was placed on the reference side of the cell. The pan lid was pierced prior to sample analysis. The sample was analyzed from −30° C. to 250° C. or 350° C. at 10° C./min. 
     C. Dynamic Vapor Sorption (DVS) 
     Automated vapor sorption (VS) data were collected on a Surface Measurement System DVS Intrinsic instrument. Samples were not dried prior to analysis. Sorption and desorption data were collected over a range from 5% to 95% RH at 10% RH increments under a nitrogen purge. The equilibrium criterion used for analysis was less than 0.0100% weight change in 5 minutes with a maximum equilibration time of 3 hours. Data were not corrected for the initial moisture content of the samples. 
     D. Solution NMR 
     NMR spectra for Compound 1 were recorded on a Bruker 400 MHz Avance III HD instrument with 5 mm PABBO BB/19F-1H/D Z-GRD Z108618 probe, or on an Avance 600 MHz NMR Spectrometer, using DMSO-d6 as a solvent. 
     NMR spectra for Compounds 2-5 were acquired with an Avance 600 MHz NMR spectrometer. The samples were prepared by dissolving given amount of sample in DMSO-d6 containing TMS. 
     E. X-Ray Fluorescence (XRF) 
     Microbeam energy dispersive X-ray fluorescence (μEDXRF) spectra were collected with a Horiba XGT-9000 equipped with a microfocus Rh X-ray source powered at 50 kV and automatically controlled current. A vacuum atmosphere was used during data collection. The silicon-strip detector (SSD) was used in the high-resolution mode, P5. 
     A monocapillary optic with a nominal focal spot of 1.2 mm was used for analysis of two areas on the sample. The analysis of one of these areas was repeated once. Quantitative analysis of chlorine was completed using fundamental parameters model in the Horiba X-ray Lab software application using a one-point calibration from a measured standard material with known chlorine content. The results were an average from the three spectra collected. 
     F. Variable Relative Humidity X-Ray Powder Diffraction (VRH-XRPD) 
     XRPD patterns were collected with a PANalytical X&#39;Pert PRO MPD diffractometer using an incident beam of Cu Kα radiation produced using a long, fine-focus source and a nickel filter. The diffractometer was configured using the symmetric Bragg-Brentano geometry. Data were collected and analyzed using Data Collector software v. 5.5. Prior to the analysis, a silicon specimen (NIST SRM 640f) was analyzed to verify the observed position of the Si 111 peak is consistent with the NIST-certified position. A specimen of the sample was packed in a nickel-coated copper well. Antiscatter slits (SS) were used to minimize the background generated by air. Soller slits for the incident and diffracted beams were used to minimize broadening from axial divergence. Diffraction patterns were collected using a scanning position-sensitive detector (X&#39;Celerator) located 240 mm from the sample and Data Collector software v. 5.5. 
     An Anton Paar temperature-humidity chamber (THC) was used while collecting in-situ XRPD patterns as a function of humidity. The temperature of the specimen was changed with a Peltier thermoelectric device located directly under the specimen holder and monitored with a platinum-100 resistance sensor located in the specimen holder. The thermoelectric device was powered and controlled by an Anton Paar TCU 50 interfaced with Data Collector. The humidity was generated with an RH-200 manufactured by VTI Inc. and carried by a flow of nitrogen gas. The humidity was monitored by a HygroClip sensor manufactured by Rotronic located next to the specimen inside the THC. 
     Example 1: N-(4-((7-cyano-1-methyl-2-((1-methyl-2-oxo-5-(trifluoromethyl)-1,2-dihydropyridin-3-yl)amino)-1H-imidazo[4,5-b]pyridin-6-yl)oxy)pyridin-2-yl)acetamide (Compound 1) 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Synthesis of compound 1.1. To a solution of benzyl alcohol (17.05 g, 157.69 mmol, 1.0 equiv) in THF (250 mL), was added sodium hydride (12.61 g, 315.38 mmol, 2 equiv) at 0° C. and stirred for 1 h. Compound 2-chloro-4-nitropyridine (25 g, 157.69 mmol, 1.0 equiv) was added and the reaction mixture was stirred at 0° C. for 2 h. The reaction mixture was transferred into ice, stirred, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 10% ethyl acetate in hexane) to afford 1.1. (20 g, 58%). MS (ES): m/z 220.13 [M+H] + . 
     Synthesis of compound 1.2. A solution of 1.1 (20 g, 91.05 mmol, 1.0 equiv) in THF (200 mL) was degassed by bubbling through a stream of argon for 10 min. Under argon atmosphere 2-dicyclohexylphosphino-2′, 4′, 6′-triisopropylbiphenyl (4.34 g, 9.105 mmol, 0.1 equiv) and tris(dibenzylideneacetone)dipalladium(0) (4.17 g, 4.55 mmol, 0.05 equiv) were added, and degassed for 5 min. To this mixture was added lithium bis(trimethylsilyl)amide solution (1 M in THF, 182 mL, 182.1 mmol, 2.0 equiv) and the reaction mixture was stirred at 65° C. for 1 h. It was cooled to room temperature, transferred into ice-water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 3% methanol in DCM) to afford 1.2 (11.2 g, 61%). MS (ES): m/z 201.2 [M+H] + . 
     Synthesis of compound 1.3. To a solution of 1.2 (11.2 g, 55.93 mmol, 1.0 equiv) and pyridine (6.3 mL, 78.30 mmol, 1.4 equiv) in DCM (110 mL) was added acetic anhydride (6.34 mL, 67.11 mmol, 1.2 equiv) at room temperature and stirred for 1 h. The reaction mixture was transferred into ice, stirred, and extracted with DCM. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 1% methanol in DCM) to afford 1.3 (6.1 g, 45%). MS (ES): m/z 243.21 [M+H] + . 
     Synthesis of compound 1.4. A mixture of compound 1.3 (6.1 g, 25.18 mmol, 1.0 equiv) and 10%/o palladium on carbon (2 g) in methanol (60 mL) was stirred under hydrogen (1 atm) for 2 h. It was filtered through a pad of Celite® and rinsed with methanol. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 5% methanol in DCM) to afford 1.4 (3.3 g, 86%). MS (ES): m/z 153.2 [M+H] + . 
     Synthesis of compound 1.5. To a solution of 5-(trifluoromethyl)pyridin-2(1H)-one (5.0 g, 30.66 mmol, 1.0 equiv) in conc. sulfuric acid (25 mL) was added fuming nitric acid (8 mL) at 0° C. The reaction mixture was stirred at 65° C. for 6 h. It was pour over crushed ice, stirred and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 2.5% methanol in DCM) to afford 1.5 (2.0 g, 31%). MS (ES): m/z 209.10 [M+H] + . 
     Synthesis of compound 1.6. To a mixture of 1.5 (1.0 g, 4.81 mmol, 1.0 equiv) and potassium carbonate (1.3 g, 9.62 mmol, 2.0 equiv) in DMF (15 mL) was stirred for 15 min before the addition of methyl iodide (1.0 g, 7.21 mmol, 1.5 equiv). The reaction mixture was stirred at 80° C. for 2 h. The reaction mixture was transferred into ice-water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 40% ethyl acetate in hexane) to afford 1.6 (0.57 g, 53%). MS (ES): m/z 223.12 [M+H] + . 
     Synthesis of compound 1.7. A mixture of compound 1.6 (0.57 g, 2.57 mmol, 1.0 equiv) and 10% palladium on carbon (0.3 g) in methanol (18 mL) was stirred under hydrogen (1 atm) for 1 h. It was filtered through a pad of Celite® and rinsed with methanol. The filtrate was concentrated under reduced pressure to obtain 1.7 (0.34 g, 68.96%). MS (ES): m/z 193.14 [M+H] + . It was used without purification. 
     Synthesis of compound 1.8. To a solution of 3,5-difluoropyridin-2-amine (10 g, 76.87 mmol, 1.0 equiv) in THF (200 mL), was added n-butyl lithium (2.5 M in hexane, 61.4 mL, 153.7 mmol, 2.0 equiv) at −78° C. and stirred for 40 min. Hexachloroethane (36.3 g, 153.7 mmol, 2.0 equiv) was added and the reaction mixture was stirred at −78° C. for 30 min. After completion of reaction, a saturated aqueous ammonium chloride solution was added carefully and stirred. The mixture was allowed to warm to room temperature and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 12% ethyl acetate in hexane) to afford 1.8 (8.0 g, 63%).  1 H NMR (DMSO-d6, 400 MHz): δ 7.98-7.94 (m, 1H), 6.48 (bs, 2H). 
     Synthesis of compound 1.9. Concentrated sulfuric acid (3 mL) was added dropwise to potassium persulfate (2.05 g, 7.6 mmol, 2.5 equiv) at room temperature and stirred for 15 min. To the mixture was added 1.8 (0.5 g, 3.04 mmol, 1.0 equiv) in portions to maintain the temperature between 30-40° C. After the addition, the reaction mixture was stirred at room temperature for 3 h. It was poured over crushed ice, stirred, basified with saturated sodium bicarbonate, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 2-3% ethyl acetate in hexane) to afford 1.9 (0.970 g, 16.41%).  1 H NMR (DMSO-d6, 400 MHz): δ 8.78 (s, 1H). 
     Synthesis of compound 1.10. To a solution of 1.9 (0.970 g, 4.99 mmol, 1.0 equiv) in acetonitrile (10 mL) was added aqueous methylamine solution (40%, 0.8 mL, 9.98 mmol, 2.0 equiv) dropwise at 0° C. The reaction mixture was stirred at room temperature for 20 min. It was transferred into ice-water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 10% ethyl acetate in hexane) to afford 1.10 (0.930 g, 91%).  1 H NMR (DMSO-d6, 400 MHz). S 7.98 (s, 1H), 7.05 (bs, 1H), 2.79 (d, 3H). 
     Synthesis of compound 1.11. To a solution of 1.10 (0.930 g, 4.52 mmol, 1.0 equiv) in DMF (10 mL) was added 1.4 (0.895 g, 5.88 mmol, 1.3 equiv) followed by sodium carbonate (0.958 g, 9.04 mmol, 2.0 equiv). The reaction mixture was stirred at 50° C. for 6 h. It was cooled to room temperature, poured into ice-water. The precipitated solids were collected by filtration, washed with water and dried under vacuum to obtain 1.11 (0.850 g, 56%). MS (ES): m/z 338.7 [M+H] + . 
     Synthesis of compound 1.12. A mixture of compound 1.11 (0.850 g, 2.52 mmol, 1.0 equiv), iron powder (0.705 g, 12.6 mmol, 5.0 equiv) and ammonium chloride (0.673 g, 12.6 mmol, 5.0 equiv) in ethanol-water (8:2, 10 mL) was stirred at 80° C. for 2 h. It was cooled to room temperature, filtered through a pad of Celite® and rinsed with ethanol. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 2.4% methanol in DCM) to afford 1.12 (0.710 g, 92%). MS (ES): m/z 308.5 [M+H] + . 
     Synthesis of compound 1.13. To a solution of 1.12 (0.150 g, 0.487 mmol, 1.0 equiv) in THF (2 mL) was added 1,1′-thiocarbonyldiimidazole (0.433 g, 2.43 mmol, 5.0 equiv). The reaction mixture was stirred at 80° C. for 1 h. It was cooled to room temperature and poured into ice-water. The precipitated solids were collected by filtration and triturated with hexane to obtain 1.13 (0.110 g, 65%). MS (ES): m/z: 350.7 [M+H] + . 
     Synthesis of compound 1.14. To a solution of 1.13 (0.110 g, 0.314 mmol, 1.0 equiv) in acetic acid (5 mL) was added aqueous hydrobromic acid (0.037 g, 0.471 mmol, 1.5 equiv) at 0° C. followed by bromine (0.200 g, 1.25 mmol, 4.0 equiv). The reaction mixture was stirred for 10 min. It was transferred into a saturated aqueous sodium bicarbonate solution, stirred, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 2.5% methanol in DCM) to afford 1.14 (0.063 g, 51%). MS (ES): m/z 397.6 [M+H] + . 
     Synthesis of compound 1.15 A mixture of 1.14 (0.220 g, 0.554 mmol, 1.0 equiv), 1.7 (0.127 g, 0.665 mmol, 1.2 equiv) and cesium carbonate (0.450 g, 1.385 mmol, 2.5 equiv) in 1,4-dioxane (12 mL) was degassed by bubbling through a stream of argon for 10 min. Under argon atmosphere 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.064 g, 0.110 mmol, 0.2 equiv) and tris(dibenzylideneacetone)dipalladium(0) (0.051 g, 0.055 mmol, 0.1 equiv) were added, and degassed for 5 min. The reaction mixture was stirred at 110° C. for 2 h. It was cooled to room temperature, transferred into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 2.3% methanol in DCM) to afford 1.15 (0.050 g, 26%). MS (ES): m/z: 508.2 [M] + . 
     Synthesis of Compound 1. A mixture of 1.15 (0.077 g, 0.151 mmol, 1.0 equiv), zinc dust (0.0019 g, 0.030 mmol, 0.2 equiv) and zinc cyanide (0.088 g, 0.755 mmol, 5.0 equiv) in dimethylacetamide (5 mL) was degassed by bubbling through a stream of Celite® for 10 min. Under argon atmosphere were added 1,1′-ferrocenediyl-bis(diphenylphosphine) (0.025 g, 0.045 mmol, 0.3 equiv) and tris(dibenzylideneacetone)dipalladium(0)(0.020 g, 0.022 mmol, 0.15 equiv), and degassed for 5 min. The reaction mixture was stirred at 170° C. in a microwave reactor for 2 h. It was cooled to room temperature, transferred into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (CombiFlash®, 2.5% methanol in DCM) to afford Compound 1 (0.025 g, 33%). MS (ES): m/z: 499.0 [M] + , LCMS purity: 99.34%, HPLC purity: 96.76%,  1 H NMR (DMSO-d6, 400 MHz): δ 10.67 (s, 1H), 9.06 (s, 1H), 8.65 (s, 1H), 8.32 (s, 1H), 8.25-8.23 (d, J=5.6 Hz, 1H), 8.19 (s, 1H), 7.75 (s, 1H), 6.76-6.75 (m, 1H), 3.96 (s, 3H), 3.66 (s, 3H), 2.06 (s, 3H). 
     Example 2: Characterization of Compound 1 
     Compound 1 was prepared generally as described in Example 1. A lot of Compound 1 (Lot I) prepared as described in Example 9 was characterized as described below and denoted Compound 1 Form 1. 
       FIG.  1    provides the XRPD pattern of Compound 1 Form 1. 
     Hygroscopicity of Compound 1 Form 1 was analyzed by dynamic vapor sorption (DVS) from 5% to 95% relative humidity ( FIG.  2    and Table 14). A total of 4.80% weight gain was observed from 5% to 95% RH, equal to 1.4 mol/mol H 2 O, with 3.36% (1.0 mol/mol H 2 O) of that weight being picked up from 45% to 55% RH. Upon desorption to 5% RH, 4.82% (1.4 mol/mol H 2 O) was lost with hysteresis evident. 3.55% (1.0 mol/mol H 2 O) of the weight loss occurred from 25% to 15% RH. The XRPD pattern of the post-DVS material was very similar to the XRPD pattern of material prepared via Example 1, but with a few missing peaks ( FIG.  3   ). 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 14 
               
               
                   
               
               
                   
                   
                   
                 Sorp  
                   
                 Desorp  
                   
               
               
                   
                 Target  
                 Sample 
                 Mass 
                 Sample 
                 Mass 
                   
               
               
                   
                 RH 
                 RH  
                 Change  
                 RH  
                 Change  
                   
               
               
                   
                 (%) 
                 (%) 
                 (%) 
                 (%) 
                 (%) 
                 Hysteresis 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cycle 1 
                 5.0 
                 5.0 
                 0.001 
                 5.5 
                 −0.011 
                   
               
               
                   
                 15.0 
                 15.5 
                 0.068 
                 16.0 
                 0.103 
                 0.036 
               
               
                   
                 25.0 
                 25.0 
                 0.118 
                 25.6 
                 3.654 
                 3.536 
               
               
                   
                 35.0 
                 34.7 
                 0.292 
                 35.3 
                 3.877 
                 3.585 
               
               
                   
                 45.0 
                 44.9 
                 0.396 
                 45.5 
                 4.084 
                 3.687 
               
               
                   
                 55.0 
                 54.9 
                 3.757 
                 55.4 
                 4.203 
                 0.446 
               
               
                   
                 65.0 
                 64.8 
                 4.049 
                 65.6 
                 4.403 
                 0.354 
               
               
                   
                 75.0 
                 74.8 
                 4.282 
                 75.4 
                 4.578 
                 0.296 
               
               
                   
                 85.0 
                 84.8 
                 4.534 
                 86.1 
                 4.677 
                 0.142 
               
               
                   
                 95.0 
                 95.0 
                 4.804 
                 95.0 
                 4.804 
                   
               
               
                   
               
            
           
         
       
     
       FIG.  3    provides an overlay XRPD pattern of Compound 1 Form 1 post-DVS material (lower) with pre-DVS material (upper). 
     Solubility Study 
     Aliquots of various solvents were added to measured amounts of Compound 1 Form 1 with agitation at ambient temperature until complete dissolution was achieved, as judged by visual observation. Compound 1 Form 1 obtained from the synthetic procedure described in Example 1 was found to show limited solubility in most of the organic solvents assessed. See Table 15 below, where A is 5-20 mg/mL; B is 1-4.9 mg/mL; and C is &lt;1 mg/mL. 
     
       
         
           
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 Solubility of Compound 1 Form 1 in Various Solvents 
               
            
           
           
               
               
               
            
               
                   
                   
                 Solubility at ambient 
               
               
                   
                 Solvent 
                 temperature (mg/mL) a   
               
               
                   
                   
               
               
                   
                 acetone 
                 C 
               
               
                   
                 ACN 
                 C 
               
               
                   
                 DCM 
                 C 
               
               
                   
                 DMA 
                 A 
               
               
                   
                 H 2 O 
                 C 
               
               
                   
                 MeOH 
                 C 
               
               
                   
                 TFE 
                 A 
               
               
                   
                 THF 
                 B 
               
               
                   
                   
               
               
                   
                   a Solubilities were calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions used or a slow rate of dissolution. If dissolution did not occur as determined by visual assessment, the value was reported as 
               
            
           
         
       
     
     Example 3: Salt Screening of Compound 1 
     In an effort to find salts of Compound 1, a salt/co-crystal screen was conducted under different conditions with various salt/co-crystal co-formers and solvent systems. 
     Compound obtained from the synthetic procedure described in Example 1 was used as the starting material for salt and cocrystal experiments. 
     For each condition, about 50-100 mg of Compound 1 was used. The results are summarized in Table 16, below: 
     
       
         
           
               
               
               
               
             
               
                 TABLE 16 
               
               
                   
               
               
                 Coformer a   
                 Conditions 
                 Observations 
                 XRPD Result 
               
               
                   
               
             
            
               
                 aspartic acid 
                 1) coformer  
                 1) pale yellow  
                 FB + aspartic  
               
               
                   
                 shiny in  
                 slurry 
                 acid 
               
               
                   
                 THF/H 2 O (10:1 
                 2) pale yellow  
                   
               
               
                   
                 THF/H 2 O) was  
                 slurry 
                   
               
               
                   
                 added to API 
                 3) off-white solids;  
                   
               
               
                   
                 2) stirred, RT,  
                 fines &amp; aggregates, 
                   
               
               
                   
                 4 d 
                 B/E 
                   
               
               
                   
                 3) positive  
                   
                   
               
               
                   
                 pressure  
                   
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) coformer  
                 1) off-white slurry 
                 FB + aspartic  
               
               
                   
                 slurry in 80:20 
                 2) yellowish slurry 
                 acid 
               
               
                   
                 acetone/H 2 O  
                 3) off-white solids;  
                   
               
               
                   
                 was added to 
                 fines &amp; aggregates, 
                   
               
               
                   
                 API 
                 B/E 
                   
               
               
                   
                 2) stirred, RT,  
                   
                   
               
               
                   
                 2 d 
                   
                   
               
               
                   
                 3) positive  
                   
                   
               
               
                   
                 pressure  
                   
                   
               
               
                   
                 filtration 
                   
                   
               
               
                 benzene sulfonic 
                 1) THF soln of  
                 1) yellow slurry 
                 Besylate  
               
               
                 acid 
                 coformer was 
                 2) yellow slurry 
                 Form A 
               
               
                   
                 added to API 
                 3) yellow solids;  
                   
               
               
                   
                 2) stirred, RT,  
                 fines &amp; aggregates,  
                   
               
               
                   
                 4 d 
                 B/E 
                   
               
               
                   
                 3) positive  
                   
                   
               
               
                   
                 pressure  
                   
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) acid soln in  
                 1) clear yellow  
                 Besylate  
               
               
                   
                 TFE was added 
                 soln 
                 Form B 
               
               
                   
                 to API 
                 2) clear soln 
                   
               
               
                   
                 2) stirred, RT,  
                 3) clear soln 
                   
               
               
                   
                 1 d 
                 4) some yellow gel  
                   
               
               
                   
                 3) stirred, −20°  
                 and yellow solids;  
                   
               
               
                   
                 C., l d 
                 fine needles &amp;  
                   
               
               
                   
                 4) FE 
                 aggregates, B/E 
                   
               
               
                 (1R)-(-)-10- 
                 1) THF soln of  
                 1) yellow slurry 
                 Compound 5  
               
               
                 camphorsulfonic 
                 coformer was 
                 2) yellow slurry 
                 Fotin A 
               
               
                 acid 
                 added to API 
                 3) yellow solids;  
                   
               
               
                   
                 2) stirred, RT,  
                 fines &amp; aggregates, 
                   
               
               
                   
                 4 d 
                 B/E 
                   
               
               
                   
                 3) positive  
                   
                   
               
               
                   
                 pressure  
                   
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) acid soln in  
                 1) clear yellow  
                 Compound 5  
               
               
                   
                 TFE was added 
                 soln 
                 Form B 
               
               
                   
                 to API 
                 2) clear soln 
                   
               
               
                   
                 2) stirred, RT,  
                 3) clear soln 
                   
               
               
                   
                 1 d 
                 4) yellow solids in  
                   
               
               
                   
                 3) stirred, −20°  
                 some yellow gel;  
                   
               
               
                   
                 C., l d 
                 long needles &amp; 
                   
               
               
                   
                 4) FE 
                 aggregates, B/E 
                   
               
               
                 1,2- 
                 1) THF soln of  
                 1) dark yellow  
                 Edisylate  
               
               
                 ethanedisulfonic 
                 coformer was 
                 slurry 
                 Form A 
               
               
                 acid 
                 added to API 
                 2) dark yellow  
                   
               
               
                   
                 2) stirred, RT,  
                 slurry 
                   
               
               
                   
                 4 d 
                 3) dark yellow  
                   
               
               
                   
                 3) positive  
                 solids; fines &amp;  
                   
               
               
                   
                 pressure  
                 aggregates, B/E 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) acid slurry in  
                 1) clear orange  
                 Edisylate  
               
               
                   
                 TFE was added  
                 soln 
                 Form B 
               
               
                   
                 to API 
                 2) clear soln 
                   
               
               
                   
                 2) stirred, RT,  
                 3) clear soln 
                   
               
               
                   
                 1 d 
                 4) yellow &amp; off- 
                   
               
               
                   
                 3) stirred, −20°  
                 white solids: fines  
                   
               
               
                   
                 C., l d 
                 &amp; aggregates, B/E 
                   
               
               
                   
                 4) FE 
                   
                   
               
               
                 ethanesulfonic 
                 1) acid was  
                 1) thick yellow  
                 Esylate Form  
               
               
                 acid 
                 added to API 
                 slurry 
                 A 
               
               
                   
                 slurry in THF 
                 2) yellow slurry 
                   
               
               
                   
                 2) stirred, RT,  
                 3) yellow solids;  
                   
               
               
                   
                 4 d 
                 fines &amp; aggregates, 
                   
               
               
                   
                 3) positive  
                 partial B/E 
                   
               
               
                   
                 pressure  
                   
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) acid added to  
                 1) clear yellow  
                 Esylate Form  
               
               
                   
                 API slurry in  
                 soln 
                 B 
               
               
                   
                 TFE 
                 2) clear soln 
                   
               
               
                   
                 2) stirred, RT,  
                 3) clear soln 
                   
               
               
                   
                 1 d 
                 4) yellow &amp; off- 
                   
               
               
                   
                 3) stirred, −20°  
                 white solids; fines, 
                   
               
               
                   
                 C., l d 
                 rosettes, &amp; 
                   
               
               
                   
                 4) FE 
                 aggregates, B/E 
                   
               
               
                 hydrobromic 
                 1) acid was  
                 l) dark yellow  
                 Compound 3  
               
               
                 acid 
                 added to API 
                 slurry 
                 Form A 
               
               
                   
                 slurry in THF 
                 2) pale pink slurry 
                   
               
               
                   
                 2) stirred, RT,  
                 3) off-white solids:  
                   
               
               
                   
                 4 d 
                 fines &amp; aggregates, 
                   
               
               
                   
                 3) positive  
                 B/E 
                   
               
               
                   
                 pressure  
                   
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) acid added to  
                 1) clear yellow  
                 Compound 3  
               
               
                   
                 API slurry in 
                 soln 
                 Form A 
               
               
                   
                 TFE 
                 2) clear soln 
                   
               
               
                   
                 2) stirred, RT,  
                 3) clear soln 
                   
               
               
                   
                 1 d 
                 4) yellow &amp; off- 
                   
               
               
                   
                 3) stirred, −20°  
                 white solids; fines, 
                   
               
               
                   
                 C., l d 
                 rosettes, &amp; 
                   
               
               
                   
                 4) FE 
                 aggregates, B/E 
                   
               
               
                 hydrochloric 
                 1) acid was  
                 1) dark yellow  
                 Compound 2  
               
               
                 acid 
                 added to API 
                 shiny 
                 Form A +  
               
               
                   
                 slurry in THF 
                 2) pale yellow  
                 minor FB 
               
               
                   
                 2) stirred, RT,  
                 slurry 
                   
               
               
                   
                 4 d 
                 3) pale yellow  
                   
               
               
                   
                 3) positive  
                 solids; fines &amp;  
                   
               
               
                   
                 pressure  
                 aggregates, B/E 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) acid was  
                 1) dark yellow  
                 Compound 2  
               
               
                   
                 added to API 
                 slurry 
                 Form A +  
               
               
                   
                 slurry in THF 
                 2) pale yellow  
                 minor peak at  
               
               
                   
                 2) stirred, RT,  
                 slurry 
                 8.54° 2θ 
               
               
                   
                 4 d 
                 3) pale yellow  
                   
               
               
                   
                 3) positive  
                 solids; fines &amp;  
                   
               
               
                   
                 pressure  
                 aggregates, B/E 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) acid added to  
                 1) clear yellow  
                 Compound 2  
               
               
                   
                 API slurry in 
                 soln 
                 Form B 
               
               
                   
                 TFE 
                 2) clear soln 
                   
               
               
                   
                 2) stirred, RT,  
                 3) clear soln 
                   
               
               
                   
                 1 d 
                 4) dark yellow  
                   
               
               
                   
                 3) stirred, −20°  
                 solids; fines &amp;  
                   
               
               
                   
                 C., l d 
                 aggregates, B/E 
                   
               
               
                   
                 4) FE 
                   
                   
               
               
                 maleic acid 
                 1) THF soln of  
                 1) pale yellow  
                 FB + peaks 
               
               
                   
                 coformer was 
                 slurry 
                   
               
               
                   
                 added to API 
                 2) pale pink slurry 
                   
               
               
                   
                 2) stirred, RT, 4 d 
                 3) off-white solids;  
                   
               
               
                   
                 3) positive  
                 fines &amp; aggregates,  
                   
               
               
                   
                 pressure  
                 B/E 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                 methane sulfonic 
                 1) acid was  
                 1) yellow slurry 
                 Compound 4  
               
               
                 acid 
                 added to API 
                 2) yellow slurry 
                 Form A 
               
               
                   
                 slurry in THF 
                 3) yellow solids;  
                   
               
               
                   
                 2) stirred, RT,  
                 fines &amp; aggregates, 
                   
               
               
                   
                 4 d 
                 partial B/E 
                   
               
               
                   
                 3) positive  
                   
                   
               
               
                   
                 pressure  
                   
                   
               
               
                   
                 filtration 
                   
                   
               
               
                 oxalic acid 
                 1) THF soln of  
                 1) pale yellow  
                 FB + peaks 
               
               
                   
                 coformer was 
                 slurry 
                   
               
               
                   
                 added to API 
                 2) pale yellow  
                   
               
               
                   
                 2) stirred, RT,  
                 slurry 
                   
               
               
                   
                 4 d 
                 3) off-white solids;  
                   
               
               
                   
                 3) positive  
                 fines &amp; aggregates,  
                   
               
               
                   
                 pressure  
                 B/E 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) coformer  
                 1) off-white slurry 
                 FB + peaks 
               
               
                   
                 slurry in 80:20 
                 2) yellowish slurry 
                   
               
               
                   
                 acetone/H 2 O  
                 3) off-white solids;  
                   
               
               
                   
                 was added to  
                 fines &amp; aggregates, 
                   
               
               
                   
                 API 
                 B/E 
                   
               
               
                   
                 2) stirred, RT,  
                   
                   
               
               
                   
                 2 d 
                   
                   
               
               
                   
                 3) positive  
                   
                   
               
               
                   
                 pressure  
                   
                   
               
               
                   
                 filtration 
                   
                   
               
               
                 phosphoric acid 
                 1) acid was  
                 1) pale yellow  
                 Phosphate  
               
               
                   
                 added to API 
                 slurry 
                 Form A 
               
               
                   
                 slurry in THF 
                 2) thick pale  
                   
               
               
                   
                 2) stirred, RT,  
                 yellow slurry 
                   
               
               
                   
                 4 d 
                 3) sticky yellow  
                   
               
               
                   
                 3) positive  
                 solids; fines &amp; 
                   
               
               
                   
                 pressure  
                 aggregates, B/E 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                   
                 1) acid added to  
                 1) off-white slurry 
                 Phosphate  
               
               
                   
                 API slurry in 
                 2) yellowish slurry 
                 Form A 
               
               
                   
                 TFE 
                 3) some yellow  
                 (slight  
               
               
                   
                 2) stirred, RT,  
                 solids (some  
                 disorder) 
               
               
                   
                 2 d 
                 deliquesced); fines 
                   
               
               
                   
                 3) positive  
                 &amp; aggregates,  
                   
               
               
                   
                 pressure  
                 partial B/E 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                 sulfuric acid 
                 1) acid added to  
                 1) clear yellow  
                 Sulfate Form  
               
               
                   
                 API slurry in 
                 soln 
                 A 
               
               
                   
                 TFE 
                 2) clear soln 
                   
               
               
                   
                 2) stirred, RT, 
                 3) clear soln 
                   
               
               
                   
                 1 d 
                 4) dark yellow  
                   
               
               
                   
                 3) stirred, −20°  
                 solids; fines &amp;  
                   
               
               
                   
                 C., l d 
                 aggregates, B/E 
                   
               
               
                   
                 4) FE 
                   
                   
               
               
                   
                 1) acid was  
                 1) dark yellow  
                 Sulfate Form  
               
               
                   
                 added to API 
                 slurry 
                 B 
               
               
                   
                 slurry in THF 
                 2) pale yellow  
                   
               
               
                   
                 2) stirred, RT,  
                 slurry 
                   
               
               
                   
                 4 d 
                 3) pale yellow  
                   
               
               
                   
                 3) positive  
                 solids; fines &amp;  
                   
               
               
                   
                 pressure  
                 aggregates, B/E 
                   
               
               
                   
                 filtration 
               
               
                   
               
               
                   a mol Compound 1/mol conformer for each experiment was 1:1 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 17 
               
             
            
               
                   
               
               
                 Characterization Data of Solid Forms 
               
            
           
           
               
               
               
            
               
                 Material/Form 
                 Technique 
                 Results 
               
               
                   
               
               
                 Compound 5  
                 XRPD 
                 successfully indexed as 1:1 with some  
               
               
                 Form C 
                   
                 excess volume in the unit cell 
               
               
                 Esylate Form  
                   1 H NMR 
                 1:1 Compound 1/ethanesulfonic acid with  
               
               
                 A 
                   
                 slight peak shifting; 0.1 mol/mol THF 
               
               
                 Compound 3  
                 XRPD 
                 successfully indexed as 1:1 HBr salt with  
               
               
                 Form A 
                   
                 a small amount of excess volume in unit  
               
               
                   
                   
                 cell. 
               
               
                   
                   1 H NMR 
                 consistent w/ chemical structure-some  
               
               
                   
                   
                 peak shifting indicative of salt formation;  
               
               
                   
                   
                 negligible amount of THF 
               
               
                   
                 DSC a   
                 large broad endo at 109.7° C.; followed by  
               
               
                   
                   
                 potential melt/decomp. w/onset at 278.1°  
               
               
                   
                   
                 C. 
               
               
                   
                 TGA b   
                 3.4% wt loss over 61 to 150° C.; 1.1  
               
               
                   
                   
                 mol/mol H 2 O 
               
               
                 Compound 2  
                 XRPD 
                 successfully indexed as unsolvated 1:1  
               
               
                 Form A 
                   
                 HCl salt 
               
               
                   
                   1 H NMR 
                 consistent w/ chemical structure—some  
               
               
                   
                   
                 peak shifting indicative of salt formation;  
               
               
                   
                   
                 negligible amount of THF 
               
               
                   
                 XRF 
                 0.83 mol Cl−/mol API 
               
               
                   
                 DSC a   
                 very shallow, broad endo at 47.0° C.;  
               
               
                   
                   
                 followed by potential melt/decomp.  
               
               
                   
                   
                 w/onset at 271.8° C. 
               
               
                   
                 TGA b   
                 0.3% wt loss over 42 to 165° C.; &lt;0.1  
               
               
                   
                   
                 mol/mol H 2 O 
               
               
                   
                 DVS 
                 wt gain 5% to 95%: 0.9468% (0.3  
               
               
                   
                   
                 mol/mol H 2 O) 
               
               
                   
                   
                 wt loss 95% to 5%: 1.0059% (0.3 mol/mol  
               
               
                   
                   
                 H 2 O) 
               
               
                   
                 post-DVS  
                 Compound 2 Form A 
               
               
                   
                 XRPD 
                   
               
               
                 Compound 4  
                 XRPD 
                 successfully indexed as unsolvated 1:1  
               
               
                 Form A 
                   
                 mesylate salt 
               
               
                   
                   1 H NMR 
                 consistent w/ 1.1:1 mol MSA/mol API— 
               
               
                   
                   
                 some peak shifting indicative of salt  
               
               
                   
                   
                 formation; 0.1 mol/mol THF 
               
               
                   
                 DSC a   
                 large broad endo at 77.7° C. then small  
               
               
                   
                   
                 endo at 254.4° C.; potential melt/decomp,  
               
               
                   
                   
                 w/ onset at 289.8° C. 
               
               
                   
                 TGA b   
                 3.3% wt loss over 44 to 114° C.; 1.1  
               
               
                   
                   
                 mol/mol H 2 O 
               
               
                 Compound 4  
                 XRPD 
                 successfully indexed as unsolvated 1:1  
               
               
                 Form B 
                   
                 mesylate saltslightly smaller unit cell than  
               
               
                   
                   
                 Compound 4 Form A 
               
               
                 Phosphate  
                   1 H NMR 
                 consistent w/ chemical structure—no peak  
               
               
                 Form A 
                   
                 shifting; negligible amount of THF 
               
               
                   
               
               
                   a Temperatures (° C.) reported were transition maxima unless otherwise stated. Temperatures were rounded to the nearest tenth of a degree. 
               
               
                   b Weight loss (%) at a certain temperature; weight changes (%) were rounded to 1 decimal place; temperatures were rounded to the nearest degree. 
               
            
           
         
       
     
     Approximate Aqueous Solubility of Selected Solid Forms 
     Aliquots of various solvents were added to measured amounts of provided compounds with agitation at ambient temperature until complete dissolution was achieved, as judged by visual observation. If dissolution occurred after the addition of the first aliquot, values were reported as “&gt;”. Results are shown in Table 18, where A is &lt;2 mg/mL; B is &lt;1 mg/mL. 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 18 
               
               
                   
                   
               
               
                   
                   
                 Estimated Aqueous 
               
               
                   
                 Source Form/Material 
                 Solubility (mg/mL) 
               
               
                   
                   
               
             
            
               
                   
                 Compound 2 Form A 
                 A 
               
               
                   
                 Besylate Form A 
                 B 
               
               
                   
                 Edisylate Form A 
                 B 
               
               
                   
                 Esylate Form A 
                 B 
               
               
                   
                 Phosphate Form A 
                 B 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 19 
               
             
            
               
                   
               
               
                 Physical Stability of Selected Solid Forms 
               
            
           
           
               
               
               
            
               
                 Source Form 
                 Condition 
                 XRPD Result 
               
               
                   
               
               
                 Besylate Form A 
                 vac. oven, RT, 5 d 
                 Besylate Form C 
               
               
                 Compound 5 Form A 
                 vac. oven, RT, 5 d 
                 Compound 5 Form C 
               
               
                 Edisylate Form A 
                 vac. oven, RT, 5 d 
                 Edisylate Form C 
               
               
                 Esylate Form A 
                 vac. oven, RT, 5 d 
                 Esylate Form A 
               
               
                 Compound 3 Form A 
                 vac. oven, 45° C., 2 d 
                 Compound 3 Form A +  
               
               
                   
                   
                 minor FB 
               
               
                 Compound 4 Form A 
                 vac. oven, 45° C., 2 d 
                 Compound 4 Form B 
               
               
                 Phosphate Form A 
                 vac. oven, RT, 5 d 
                 Phosphate Form A 
               
               
                   
               
            
           
         
       
     
     Example 4: Compound 2 (Hydrochloric Acid×Compound 1) 
     
       
         
         
             
             
         
       
     
     Compound 2 Form A 
     Compound 1 (93.0 mg) was slurried in THF (2 mL). Concentrated HCl (16.0 PL) was added to the slurry. The slurry was stirred at ambient temperature for 4 days. Solids were isolated by filtration to provide Compound 2 Form A. 
     X-ray fluorescence was used to determine the approximate stoichiometry of Cl −  in Compound 2 Form A. This was determined to be approximately 0.83 mol Cl − /mol Compound 1. 
     DVS was also obtained for Compound 2 Form A, displaying a weight gain of only 0.95%, or 0.3 mol/mol H 2 O, up to 95% RH and a weight loss of 1.01% upon desorption to 5% RH ( FIG.  6    and Table 20). No hysteresis was observed. Aqueous solubility of Compound 2 Form A was visually approximated to be less than 2 mg/mL. The remaining solids were stirred for 1 day and collected. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 20 
               
               
                   
               
               
                   
                 Target  
                 Sample 
                 Sorp Mass 
                 Sample 
                 Desorp  
                   
               
               
                   
                 RH 
                 RH  
                 Change  
                 RH  
                 Mass 
                 Hyster- 
               
               
                   
                 (%) 
                 (%) 
                 (%) 
                 (%) 
                 Change (%) 
                 esis 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cycle  
                 5.0 
                  5.0 
                 0.0009 
                  5.6 
                 −0.0582 
                   
               
               
                 1 
                 15.0 
                 15.5 
                 0.0521 
                 16.1 
                 0.0326 
                 −0.0195 
               
               
                   
                 25.0 
                 24.9 
                 0.0998 
                 25.6 
                 0.0900 
                 −0.0098 
               
               
                   
                 35.0 
                 34.6 
                 0.1539 
                 35.4 
                 0.1559 
                   0.0020 
               
               
                   
                 45.0 
                 44.8 
                 0.2007 
                 45.6 
                 0.2304 
                   0.0297 
               
               
                   
                 55.0 
                 54.7 
                 0.2634 
                 55.4 
                 0.3159 
                   0.0525 
               
               
                   
                 65.0 
                 64.7 
                 0.3387 
                 65.5 
                 0.4283 
                   0.0896 
               
               
                   
                 75.0 
                 74.7 
                 0.5032 
                 75.3 
                 0.5577 
                   0.0545 
               
               
                   
                 85.0 
                 84.6 
                 0.6403 
                 85.6 
                 0.6871 
                   0.0468 
               
               
                   
                 95.0 
                 95.0 
                 0.9477 
                 95.0 
                 0.9477 
                   
               
               
                   
               
            
           
         
       
     
       FIG.  4    provides the XRPD pattern of the Compound 2 Form A. 
       FIG.  5    provides the TGA/DSC curves of Compound 2 Form A. 
       FIG.  7    depicts a XRPD overlay of Compound 2 Form A post-DVS material (lower) with pre-DVS material (upper). 
     Example 5: Compound 3 (Hydrobromic Acid×Compound 1) 
     
       
         
         
             
             
         
       
     
     Compound 3 Form A 
     Compound 1 (83.8 mg) was slurried in THF (2 mL). Concentrated HBr (19.5 μL) was added to the slurry. The slurry was stirred at ambient temperature for 4 days. Solids were isolated by filtration to provide Compound 3 Form A. 
       FIG.  8    provides the XRPD pattern of the Compound 3 Form A. 
       FIG.  9    provides the TGA/DSC curves of Compound 3 Form A. 
     Example 6: Compound 4 (Methanesulfonic Acid×Compound 1) 
     
       
         
         
             
             
         
       
     
     Compound 4 Form A 
     Compound 1 (81.0 mg) was slurried in THF (2 mL). Methanesulfonic acid (11.0 μL) was added to the slurry. The slurry was stirred at ambient temperature for 4 days. Solids were isolated by filtration to provide Compound 4 Form A. 
       FIG.  10    provides the XRPD pattern of Compound 4 Form A. 
       FIG.  11    provides the TGA/DSC curves of Compound 4 Form A. 
     Compound 4 Form B 
     Compound 4 Form A material was placed in a 45° C. vacuum oven in a loosely capped vial for 2 days. The vial was capped and cooled to ambient temperature over desiccant to provide Compound 4 Form B. 
       FIG.  12    provides the XRPD pattern of Compound 4 Form B. 
     Example 7: Compound 5 ((1R)-(−)-10-camphorsulfonic Acid×Compound 1) 
     
       
         
         
             
             
         
       
     
     Compound 5 Form C 
     (1R)-(−)-10-camphorsulfonic acid (39.2 mg) was dissolved in THF (2 mL) with sonication. The coformer solution was added to Compound 1 (77.7 mg). The slurry was stirred at ambient temperature for 4 days. Solids were isolated by filtration and further dried in a vacuum oven at ambient temperature for 5 days to provide Compound 5 Form C. 
       FIG.  13    provides the XRPD pattern of Compound 5 Form C. 
     Example 8: Biological Characterization of Provided Compounds 
     JAK2 Binding Assay 
     JAK2 (JH1domain-catalytic, Y1007F,Y1008F) kinase was expressed as N-terminal fusion to the DNA binding domain of NFkB in transiently transfected HEK293 cells and subsequently tagged with DNA for qPCR detection. Streptavidin-coated magnetic beads were treated with biotinylated small molecule ligands for 30 minutes at room temperature to generate affinity resins for kinase assays. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mmol/L DTT) to remove unbound ligand and to reduce nonspecific phage binding. Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1×binding buffer (1×PBS, 0.05% Tween 20, 0.1% BSA, 1 mmol/L DTT). Test compound was prepared as 111×stocks in 100% DMSO and directly diluted into the assay wells. All reactions were performed in polypropylene 384-well plates in a final volume of 0.02 mL. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 μmol/L non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluate was measured by qPCR. Compound 1 as prepared by Example 1 was found to have a K d &lt;10 nM. 
     JAK Family Selectivity Assays 
     Provided compounds are evaluated for selectivity by comparing their JAK2 binding affinity (K d ) in the above JAK2 Binding Assay with their binding affinity (K d ) for one or more other kinases. Binding affinity for other kinases is determined as follows: Kinase-tagged T7 phage strains are prepared in an  E. coli  host derived from the BL21 strain.  E. coli  are grown to log-phase and infected with T7 phage and incubated with shaking at 32° C. until lysis. The lysates are centrifuged and filtered to remove cell debris. The remaining kinases are produced in HEK-293 cells and subsequently tagged with DNA for qPCR detection. Streptavidin-coated magnetic beads are treated with biotinylated small molecule ligands for 30 minutes at room temperature to generate affinity resins for kinase assays. The liganded beads are blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions are assembled by combining kinases, liganded affinity beads, and test compounds in 1×binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds are prepared as 111×stocks in 100% DMSO. Kds are determined using an 11-point 3-fold compound dilution series with three DMSO control points. All compounds for Kd measurements are distributed by acoustic transfer (non-contact dispensing) in 100/6 DMSO. The compounds are then diluted directly into the assays such that the final concentration of DMSO is 0.9%. All reactions are performed in polypropylene 384-well plate. Each has a final volume of 0.02 ml. The assay plates are incubated at room temperature with shaking for 1 hour and the affinity beads are washed with wash buffer (1×PBS, 0.05% Tween 20). The beads are then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates is measured by qPCR. Compounds that exhibit a better binding affinity for JAK2 compared to one or more other kinases are considered to be JAK2-selective compounds. In some embodiments, provided compounds may be JAK2-selective over one or more of the following kinases: JAK1, JAK3, and Tyk2. 
     SET2-pSTAT5 Cellular Assay 
     This assay measures inhibition of JAK2-mediated pSTAT5 signaling in constitutively active essential thrombocytopenia cells carrying the V617F mutation. Cells are harvested from a flask into cell culture medium, and the number of cells is counted. The cells are diluted with culture medium and 100 μL of cell suspension (50000/well) is added into each well of a 96-well cell culture plate. A solution of test compound is added to the assay plate. The plates are covered with a lid and placed in a 37° C. 5% CO 2  incubator for 4 hours. After 4 hours, the cells are spun, and the cell pellets are re-suspended with 100 μL cold PBS. Then, the cells are spun again at 4° C. and 4000 rpm for 5 min. PBS is aspirated, and 25 μL lysis buffer (with protease and phosphatase inhibitor cocktail) is added to each cell pellet. The cell lysate is shaken at 4° C. for 20 min to fully lyse the cells. The cell lysate is spun at 4° C. and 4000 rpm for 15 min, and then the supernatant is transferred into a new plate and stored at −80° C. Meso-scale discovery (MSD) is used to analyze plates as follows: a standard MSD plate is coated with capture antibody in PBS (40 μL/well) and is incubated at 4° C. overnight with shaking. The MSD plate is washed three times with 150 μL/well of 1×MSD Wash Buffer (Tris-buffered saline with 0.1% Tween® 20 detergent, TBST). The MSD plates are then blocked with 150 μL of blocking buffer (5% BSA in TBST) and shaken for 1 h at room temperature and 600 rpm. The MSD plate is washed three times with 150 μL/well of 1×MSD Wash Buffer (TBST). Sample lysates are then added to MSD plates (25 μL/well) and shaken for 1 h at room temperature and 600 rpm. The MSD plate is washed three times with 150 μL/well of 1×MSD Wash Buffer (TBST). Detection antibody (prepared in Antibody Detection buffer, 1% BSA in 1×TBST) is then added to the MSD plates, and they are shaken for 1 h at room temperature and 600 rpm. The MSD plate is washed three times with 150 μL/well of 1×MSD Wash Buffer (TBST). A secondary detection antibody (prepared in Antibody Detection buffer, 1% BSA in 1×TBST) is then added to the MSD plates, and they are shaken for 1 h at room temperature and 600 rpm. The MSD plate is washed three times with 150 μL/well of 1×MSD Wash Buffer (TBST). MSD reading buffer (1×) is added to the plates (150 μL/well), and they are diluted from 4× with water. The plates are imaged using an MSD imaging instrument according to the manufacturer&#39;s instructions. 
     Caco2 Permeability Assay 
     Preparation of Caco-2 Cells: 50 μL and 25 mL of cell culture medium are added to each well of a Transwell® insert and reservoir, respectively. Then, the HTS Transwell® plates are incubated at 37° C., 5% CO 2  for 1 hour before cell seeding. Caco-2 cell cells are diluted to 6.86×105 cells/mL with culture medium, and 50 μL of cell suspension are dispensed into the filter well of the 96-well HTS Transwell® plate. Cells are cultivated for 14-18 days in a cell culture incubator at 37° C., 5% CO 2 , 95% relative humidity. Cell culture medium is replaced every other day, beginning no later than 24 hours after initial plating. 
     Preparation of Stock Solutions: 10 mM stock solutions of test compounds are prepared in DMSO. The stock solutions of positive controls are prepared in DMSO at the concentration of 10 mM. Digoxin and propranolol are used as control compounds in this assay. 
     Assessment of Cell Monolayer Integrity: Medium is removed from the reservoir and each Transwell® insert and is replaced with prewarmed fresh culture medium. Transepithelial electrical resistance (TEER) across the monolayer is measured using Millicell Epithelial Volt-Ohm measuring system (Millipore, USA). The Plate is returned to the incubator once the measurement is done. The TEER value is calculated according to the following equation: TEER measurement (ohms)×Area of membrane (cm 2 )=TEER value (ohm·cm 2 ). A TEER value greater than 230 ohm·cm 2  indicates a well-qualified Caco-2 monolayer. 
     Assay Procedure: The Caco-2 plate is removed from the incubator and washed twice with pre-warmed HBSS (10 mM HEPES, pH 7.4), and then incubated at 37° C. for 30 minutes. The stock solutions of control compounds are diluted in DMSO to get 1 mM solutions and then diluted with HBSS (10 mM HEPES, pH 7.4) to get 5 μM working solutions. The stock solutions of the test compounds are diluted in DMSO to get 1 mM solutions and then diluted with HBSS (10 mM HEPES and 4% BSA, pH 7.4) to get 5 μM working solutions. The final concentration of DMSO in the incubation system is 0.5%. To determine the rate of drug transport in the apical to basolateral direction. 75 μL of 5 μM working solutions of test compounds are added to the Transwell® insert (apical compartment) and the wells in the receiver plate (basolateral compartment) are filled with 235 μL of HBSS (10 mM HEPES and 4% BSA, pH 7.4). To determine the rate of drug transport in the basolateral to apical direction, 235 μL of 5 μM working solutions of test compounds are added to the receiver plate wells (basolateral compartment) and then the Transwell® inserts (apical compartment) are filled with 75 μL of HBSS (10 mM HEPES and 4% BSA, pH 7.4). Time 0 samples are prepared by transferring 50 μL of 5 μM working solution to wells of the 96-deepwell plate, followed by the addition of 200 μL cold methanol containing appropriate internal standards (IS). The plates are incubated at 37° C. for 2 hours. At the end of the incubation, 50 μL samples from donor sides (apical compartment for Ap→Bl flux, and basolateral compartment for Bl→Ap) and receiver sides (basolateral compartment for Ap→Bl flux, and apical compartment for Bl→Ap) are transferred to wells of a new 96-well plate, followed by the addition of 4 volume of cold acetonitrile or methanol containing appropriate internal standards (IS). Samples are vortexed for 5 minutes and then centrifuged at 3,220 g for 40 minutes. An aliquot of 100 μL of the supernatant is mixed with an appropriate volume of ultra-pure water before LC-MS/MS analysis. To determine the Lucifer Yellow leakage after 2 hour transport period, stock solution of Lucifer yellow is prepared in ultra-pure water and diluted with HBSS (10 mM HEPES, pH 7.4) to reach the final concentration of 100 μM. 100 μL of the Lucifer yellow solution is added to each Transwell® insert (apical compartment), followed by filling the wells in the receiver plate (basolateral compartment) with 300 μL of HBSS (10 mM HEPES, pH 7.4). The plates are incubated at 37° C. for 30 minutes. 80 μL samples are removed directly from the apical and basolateral wells (using the basolateral access holes) and transferred to wells of new 96 wells plates. The Lucifer Yellow fluorescence (to monitor monolayer integrity) signal is measured in a fluorescence plate reader at 485 nM excitation and 530 nM emission. 
     Cytotoxicity Assay 
     HEK293T cells are harvested from flask into cell culture medium, and then the cells are counted. The cells are diluted with culture medium to the desired density, and 40 μL of cell suspension is added into each well of a 384-well cell culture plate. The plates are covered with a lid and spun at room temperature at 1,000 RPM for 1 minute and then transferred into 37° C. 5% CO 2  incubator overnight. Test compounds are dissolved at 10 mM DMSO stock solution. 45 μL of stock solution is then transferred to a 384 PP-plate. A 3-fold, 10-point dilution is performed via transferring 15 μL compound into 30 μL DMSO by using TECAN (EVO200) liquid handler. The plates are spun at room temperature at 1,000 RPM for 1 minute and shaken on a plate shaker for 2 minutes. 40 nL of diluted compound is transferred from compound source plate into the cell plate by using liquid handler Echo550. After compound treatment for 48 hours, CTG detection is performed for compound treatment plates: the plates are removed from incubators and equilibrated at room temperature for 15 minutes. 30 μL of CellTiter-Glo reagent is added into each well to be detected. The plates are then placed at room temperature for 30 min followed by reading on EnVision. Inhibition activity is calculated with the following formula: % Inhibition=100×(LumHC−LumSample)/(LumHC−LumLC), wherein HC is reading obtained from cells treated with 0.1% DMSO only and LC is reading from cells treated with 10 μL staurosporine. IC 50  values are calculated using XLFit (equation 201). 
     Hepatocyte Stability Assay 
     10 mM stock solutions of test compound and positive control are prepared in DMSO. Stock solutions are diluted to 100 μM by combining 198 μL of 50% acetonitrile/50% water and 2 μL of 10 mM stock solution. Verapamil is used as positive control in the assay. Vials of cryopreserved hepatocytes are thawed in a 37° C. water bath with gently shaking. The contents are poured into the 50 mL thawing medium conical tube. Vials are centrifuged at 100 g for 10 minutes at room temperature. Thawing medium is aspirated and hepatocytes are re-suspended with serum-free incubation medium to yield ˜1.5×106 cells/mL. Cell viability and density are counted using a Trypan Blue exclusion, and then cells are diluted with serum-free incubation medium to a working cell density of 0.5×106 viable cells/mL. A portion of the hepatocytes at 0.5×106 viable cells/mL are boiled for 5 min prior to adding to the plate as negative control to eliminate the enzymatic activity so that little or no substrate turnover should be observed. Aliquots of 198 μL hepatocytes are dispensed into each well of a 96-well non-coated plate. The plate is placed in the incubator for approximately 10 minutes. Aliquots of 2 μL of the 100 μM test compound and 2 μL positive control are added into respective wells of a non-coated 96-well plate to start the reaction. The final concentration of test compound is 1 μM. This assay is performed in duplicate. The plate is incubated in the incubator for the designed time points. 25 μL of contents are transferred and mixed with 6 volumes (150 μL) of cold acetonitrile with internal standard (100 nM alprazolam, 200 nM labetalol, 200 nM caffeine and 200 nM diclofenac) to terminate the reaction at time points of 0, 15, 30, 60, 90 and 120 minutes. Samples are centrifuged for 25 minutes at 3,220 g and aliquots of 150 μL of the supernatants are used for LC-MS/MS analysis. 
     Kinetic Solubility Assay 
     Stock solutions of test compounds are prepared in DMSO at the concentration of 10 mM, and a stock solution of control compound is prepared in DMSO at the concentration of 30 mM. Diclofenac is used as positive control in the assay. 30 μL stock solution of each compound is placed into their a 96-well rack, followed by adding 970 μL of PBS at pH 4.0 and pH 7.4 into each vial of the cap-less solubility sample plate. This study is performed in duplicate. One stir stick is added to each vial and then vials are sealed using a molded PTDE/SIL 96-Well Plate Cover. The solubility sample plate is transferred to the Thermomixer comfort plate shaker and incubated at RT for 2 hours with shaking at 1100 rpm. After 2 hours incubation, stir sticks are removed using a big magnet and all samples from the solubility sample plate are transferred into the filter plate. All the samples are filtered by vacuum manifold. The filtered samples are diluted with methanol. Samples are analyzed by LC-MS/MS and quantified against a standard of known concentration in DMSO using LC coupled with Mass spectral peak identification and quantitation. The solubility values of the test compounds are calculated as follows, wherein INJ VOL is injection volume, DF is dilution factor, and STD is standard: 
     
       
         
           
             
               [ 
               Sample 
               ] 
             
             = 
             
               
                 
                   AREA 
                   Sample 
                 
                 × 
                 INJ 
                 ⁢ 
                    
                 
                   VOL 
                   Std 
                 
                 × 
                 
                   DF 
                   Sample 
                 
                 × 
                 
                   [ 
                   STD 
                   ] 
                 
               
               
                 
                   AREA 
                   Std 
                 
                 × 
                 INJ 
                 ⁢ 
                    
                 
                   VOL 
                   Sample 
                 
               
             
           
         
       
     
     Plasma Protein Binding Assay 
     Working solutions of test compounds and control compound are prepared in DMSO at the concentration of 200 μM, and then the working solutions are spiked into plasma. The final concentration of compound is 1 μM. The final concentration of DMSO is 0.5%. Ketoconazole is used as positive control in the assay. Dialysis membranes are soaked in ultrapure water for 60 minutes to separate strips, then in 20% ethanol for 20 minutes, finally in dialysis buffer for 20 minutes. The dialysis set up is assembled according to the manufacturer&#39;s instruction. Each Cell is with 150 μL of plasma sample and dialyzed against equal volume of dialysis buffer (PBS). The assay is performed in duplicate. The dialysis plate is sealed and incubated in an incubator at 37° C. with 5% CO 2  at 100 rpm for 6 hours. At the end of incubation, 50 μL of samples from both buffer and plasma chambers are transferred to wells of a 96-well plate. 50 μL of plasma is added to each buffer samples and an equal volume of PBS is supplemented to the collected plasma sample. 400 μL of precipitation buffer acetonitrile containing internal standards (IS, 100 nM alprazolam, 200 nM labetalol, 200 nM imipramine and 2 μM ketoplofen) is added to precipitate protein and release compounds. Samples are vortexed for 2 minutes and centrifuged for 30 minutes at 3,220 g. Aliquot of 50 μL of the supernatant is diluted by 150 μL acetonitrile containing internal standards: ultra-pure H 2 O=1:1, and the mixture is used for LC-MS/MS analysis. 
     Example 9: Preparation and Characterization of Additional Lots of Compound 1 
     Three lots of Compound 1 were prepared and used for salt and polymorph screening (e.g., as described in the Examples herein). 
     Lot I 
     Lot I was prepared generally according to Example 1, with the last step as follows. To a solution of 1.15 (12.5 g, 24.6 mmol, 1.0 equiv) in dimethylacetamide (60 mL) were added zinc dust (0.368 g, 5.67 mmol, 0.23 equiv), zinc cyanide (1.69 g, 14.5 mmol, 0.59 equiv), 1,1′-ferrocenediyl-bis(diphenylphosphine) (3.4 g, 6.15 mmol, 0.25 equiv), and tris(dibenzylideneacetone)dipalladium(0) (2.8 g, 3.07 mmol, 0.125 equiv). The mixture was degassed for 10 min. The reaction mixture was stirred in a sealed tube at 205-210° C. for 4-5 h. After completion of reaction, the reaction mixture was transferred into ice-cold water and extracted with dichloromethane. The organic layers were combined, washed with brine solution, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified by column chromatography using 2.0% methanol in dichloromethane as eluent to obtain Compound 1 (5 g, 40.76% yield). 
     Based on XRPD analysis, Lot I was a mixture of hydrate Form A with a minor amount of anhydrous Form B ( FIG.  14 A , top). 
     Additional characterization of Lot I is described in Example 2 above. 
     Lot II 
     Lot II was prepared generally according to Example 1, with the last step as follows: To a solution of 1.15 (23 g, 45.36 mmol, 1.0 equiv) in N-methyl-2-pyrrolidone (115 mL) was added zinc dust (0.678 g, 10.4 mmol, 0.23 equiv), zinc cyanide (3.13 g, 26.7 mmol, 0.59 equiv), 1,1′-ferrocenediyl-bis(diphenylphosphine) (6.28 g, 11.3 mmol, 0.25 equiv) and tris(dibenzylideneacetone)dipalladium(0) (5.18 g, 5.67 mmol, 0.125 equiv). The mixture was degassed for 10 min. The reaction mixture was stirred in a sealed tube at 140° C. for 4-5 h. After completion of reaction, the reaction mixture transferred into ice-cold water and extracted with dichloromethane. The organic layers were combined, washed with brine solution, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified by column chromatography using 2.0% methanol in dichloromethane as eluent to obtain Compound 1 (10 g, 44.30% yield). 
     Based on XRPD analysis, Lot 11 was a mixture of Form B and Form O with a minor amount of Form A ( FIG.  14 A , middle). By solution  1 H NMR, a sample of Lot II was consistent with the chemical structure of Compound 1 and showed no organic solvents. 
     DVS analysis of Lot II was performed ( FIG.  15    and Table 21). Lot II displayed a much larger weight gain compared to Lot I. From 5% to 95% RH, a 9.4% weight gain was observed which was calculated to be approximately 2.9 mol/mol H 2 O. The sharpest increase in water uptake occurred from 25% to 55% which accounted for 6.7% (˜2.0 mol/mol H 2 O) of the total weight gain. Upon desorption from 95% to 5% RH, 9.4% weight was lost which is equivalent to ˜2.9 mol/mol H 2 O. Hysteresis was observed with desorption, and the sharpest decrease in weight occurring from 35% RH to 15% RH. The XRPD pattern of the post-DVS material removed at low RH conditions was shown to be mostly Form B with some peaks attributed to Form O present ( FIG.  16   ). 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 21 
               
               
                   
               
               
                   
                 Target  
                   
                 Sorp Mass 
                   
                 Desorp  
                   
               
               
                   
                 RH 
                 Sample 
                 Change  
                 Sample 
                 Mass 
                 Hyster- 
               
               
                   
                 (%) 
                 RH (%) 
                 (%) 
                 RH (%) 
                 Change (%) 
                 esis 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cycle 1 
                 5.0 
                 4.7 
                 0.000 
                 5.1 
                 −0.019 
                   
               
               
                   
                 15.0 
                 15.2 
                 0.152 
                 15.6 
                 0.332 
                 0.180 
               
               
                   
                 25.0 
                 24.7 
                 0.250 
                 25.0 
                 5.623 
                 5.373 
               
               
                   
                 35.0 
                 34.2 
                 1.468 
                 34.5 
                 6.984 
                 5.516 
               
               
                   
                 45.0 
                 44.1 
                 4.861 
                 44.6 
                 7.374 
                 2.513 
               
               
                   
                 55.0 
                 53.8 
                 6 994 
                 54.3 
                 7.842 
                 0.848 
               
               
                   
                 65.0 
                 64.0 
                 7.697 
                 64.7 
                 8.505 
                 0.808 
               
               
                   
                 75.0 
                 74.3 
                 8.454 
                 74.9 
                 8.972 
                 0.518 
               
               
                   
                 85.0 
                 84.5 
                 9.042 
                 85.9 
                 9.206 
                 0.164 
               
               
                   
                 95.0 
                 94.5 
                 9.408 
                 94.5 
                 9.408 
                   
               
               
                   
               
            
           
         
       
     
     Kinetic solubility of Compound 1 Lot II was visually estimated at ambient temperature (Table 22). Aliquots of various solvents were added to weighed samples of Compound 1 Lot II with agitation at ambient temperature until complete dissolution was achieved, as judged by visual observation. If dissolution occurred after the addition of the first aliquot, values were reported as “&gt;”. If dissolution did not occur, values were reported as “&lt;”. 
     At ambient temperature, limited solubility values (1-20 mg/mL) were observed for AcOH, DMF, DMSO, 50:50 MeOH/DCM, 50:50 MeOH/CHCl 3 , NMP, TFE, and 50:50 TFE/H 2 O. In THF, initially sample did not appear to completely dissolve at a concentration of 1 mg/mL. However, solids appeared to be almost completely dissolved when left at ambient temperature overnight indicating a solubility of at least 1 mg/mL. The only solvent that displayed a solubility of greater than 20 mg/mL was HFIPA (84 mg/mL). See Table 22, where A is 5-20 mg/mL; B is 1-4.9 mg/mL; and C is &lt;1 mg/mL. 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 22 
               
               
                   
                   
               
               
                   
                 Solvent a   
                 Solubility (mg/mL) b   
               
               
                   
                   
               
             
            
               
                   
                 Acetone 
                 C 
               
               
                   
                 50:50 acetone/water 
                 B 
               
               
                   
                 ACN 
                 C 
               
               
                   
                 AcOH 
                 A 
               
               
                   
                 CHCl 3   
                 C 
               
               
                   
                 DCM 
                 C 
               
               
                   
                 DMA 
                 A 
               
               
                   
                 DMF 
                 B 
               
               
                   
                 DMSO 
                 A 
               
               
                   
                 Ethylene glycol 
                 C 
               
               
                   
                 HFIPA 
                 A 
               
               
                   
                 H 2 O 
                 C 
               
               
                   
                 MeOH 
                 C 
               
               
                   
                 50:50 MeOH/DCM 
                 A 
               
               
                   
                 50:50 MeOH/CHCl 3   
                 A 
               
               
                   
                 50:50 MeOH/H 2 O 
                 C 
               
               
                   
                 NMP 
                 A 
               
               
                   
                 TFE 
                 A 
               
               
                   
                 THF 
                 B c   
               
               
                   
                 50:50 DMA/H 2 O 
                 C 
               
               
                   
                 5:95 HFIPA/H 2 O 
                 C 
               
               
                   
                 50:50 TFE/H 2 O 
                 B 
               
               
                   
                 50:50 THF/H 2 O 
                 B 
               
               
                   
                   
               
               
                   
                   a Solvent ratios are v/v. 
               
               
                   
                   b Solubilities are calculated based on the total solvent used to give a solution. Actual solubilities may be greater because of the volume of solvent portions used or a slow rate of dissolution. 
               
               
                   
                   c Solution was almost completely clear after 24 h. 
               
            
           
         
       
     
     Lot III 
     Lot III was prepared using a different synthetic route than that described in Example 1. The last step was performed as follows: 
     
       
         
         
             
             
         
       
     
     Synthesis of Compound 1. To solution of 9.1 (15 g, 32.87 mmol, 1.0 equiv) in tetrahydrofuran (350 mL) and N,N-dimethylformamide (150 mL) was added triethylamine (13.7 mL, 98.61 mmol, 3.0 equiv), cooled to 0° C., followed by addition of acetyl chloride (3.51 mL, 49.30 mmol, 1.5 equiv), and stirred at room temperature for 1 h. After completion of reaction, the reaction mixture was transferred into water and extracted with ethyl acetate. The organic layers were combined, washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was taken up in methanol (200 mL), and potassium carbonate (13.6 g, 98.61 mmol, 3.0 equiv) was added. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was filtered and washed with 20% methanol in dichloromethane. The filtrate was concentrated under reduced pressure. The crude material was purified by column chromatography using 3.5% methanol in dichloromethane as eluent to give Compound 1 (10 g, 61.04% yield). MS (ES): m/z: 499.2 [M+H] + ,  1 H NMR (DMSO-d6, 400 MHz): δ 10.66 (s, 1H), 9.04 (s, 1H), 8.66 (s, 1H), 8.32 (s, 1H), 8.26-8.24 (d, J=5.6 Hz, 1H), 8.19 (s, 1H), 7.76 (s, 1H), 6.77-6.76 (m, 1H), 3.97 (s, 3H), 3.67 (s, 3H), 2.07 (s, 3H). 
     Based on XRPD analysis, Lot III was a mixture of Form O with a minor amount of Form B ( FIG.  14 A , bottom). Approximately 0.24 mol/mol EtOAc and negligible amounts of Et 2 O and DCM were present in Lot III, as judged by NMR, suggesting that its primary component Form O could be solvated. Lot III was analyzed on a combination thermogravimetric analysis and differential scanning calorimetry instrument ( FIG.  17   ). A 5% weight loss over 42° C. to 185° C. was observed by TGA. A sharp endotherm was also shown in the DSC at 308.8° C. 
     Example 10: Polymorph Screening of Compound 1 
     Compound 1 Lots I and II were used for stable form and polymorph screening experiments. Sixteen slurry experiments were done at ambient temperature and 50° C. to target a stable form. The polymorph landscape was evaluated primarily using kinetic techniques such as vapor stressing, evaporation, and cooling. Generated solids were observed by polarized light microscopy (PLM) and/or analyzed by X-ray powder diffraction (XRPD). In some instances, solids were analyzed wet to increase the likelihood of identifying labile hydrated or solvated forms. To investigate the physical stability of these solvated/hydrated materials, samples were placed under vacuum at ambient and elevated temperature (Table 25). Water activity slurries and relative humidity stressing were also utilized to further evaluate the propensity of Compound 1 to form hydrates. Fifteen forms were identified from these studies. Most identified forms were solvates, evidencing Compound 1&#39;s propensity toward polymorphism and solvation. Polymorph screening experiments were typically performed on a scale of about 50 mg of Compound 1. 
     The following techniques were used: 
     Fast evaporation: Solutions of Compound 1 were prepared in dry HFIPA and dry TFE. Solutions were filtered with 0.2 μm PTFE syringe filters and left open at ambient conditions until there was no apparent solvent. Dry solids were analyzed by XRPD. 
     Drying experiments: Damp and solvated Compound 1 materials were placed in vacuum ovens set to ambient temperature or 80° C. for 1 day. Dried solids were analyzed by XRPD. 
     Relative humidify jar experiments: Solid Compound 1 was placed in relative humidity jars containing saturated solutions of various salts to maintain a desired relative humidity level at 25° C. One sample of Compound 1 was placed in a jar containing P205 in an effort to maintain 0% RH. 
     Slow cooling: A solution of Compound 1 was prepared in THC at 55° C. The solution was filtered, hot, with a 0.2 μm nylon filter into a wart vial. The vial was capped and returned to the heat block with the heat turned off to slowly cool to ambient temperature. Clear solution was decanted and solids were analyzed by XRPD. 
     Slurrying experiments: Saturated solutions of Compound 1 were prepared in various solvents and aqueous solvent mixtures. Mixtures were stirred at elevated and ambient temperatures for the given length of time. Solids were collected by the stated technique. 
     The results of these experiments are summarized in Table 23, Table 24, Table 25, and Table 26. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 23 
               
               
                   
               
               
                   
                   
                   
                 XRPD  
               
               
                 Solvent a   
                 Conditions b   
                 Observations 
                 Results 
               
               
                   
               
             
            
               
                 AcOH 
                 1) slurry, RT, 10 d 
                 1) off-white slurry 
                 C 
               
               
                   
                 2) positive pressure  
                 2) white solids, fine &amp; 
                   
               
               
                   
                 filtration 
                 aggregates, partial B/E 
                   
               
               
                 Dry  
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 N 
               
               
                 CPME 
                 2) positive pressure  
                 2) off-white solids 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                 Dry DMA 
                 1) slurry, RT, 10 d 
                 1) orange slurry 
                 D (analyzed 
               
               
                   
                 2) positive pressure  
                 2) off-white solids; fine  
                 damp) c   
               
               
                   
                 filtration 
                 &amp; aggregates, B/E 
                   
               
               
                 Dry DMF 
                 1) slurry, RT, 10 d 
                 1) pink slurry 
                 G (analyzed 
               
               
                   
                 2) positive pressure  
                 2) off-white solids; fine  
                 damp) f   
               
               
                   
                 filtration 
                 &amp; aggregates, B/E 
                   
               
               
                 Dry  
                 1) slurry, RT, 10 d 
                 1) orange slurry 
                 E (analyzed 
               
               
                 DMSO 
                 2) positive pressure  
                 2) off-white solids; fine  
                 damp) d   
               
               
                   
                 filtration 
                 &amp; aggregates, B/E 
                   
               
               
                 EtOAc 
                 1) slurry, RT, 3 d 
                 1) off-white slurry 
                 P 
               
               
                   
                 2) positive pressure  
                 2) off-white solids; fine  
                   
               
               
                   
                 filtration 
                 &amp; aggregates, B/E 
                   
               
               
                 EtOH 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 Disordered 
               
               
                   
                 2) positive pressure  
                 2) off-white solids 
                 mixture of 
               
               
                   
                 filtration 
                   
                 peaks 
               
               
                 Dry IPA 
                 1) slurry, RT, 14 d 
                 1) off-white slurry 
                 B + peaks 
               
               
                   
                 2) positive pressure  
                 2) off-white solids, fine  
                   
               
               
                   
                 filtration 
                 &amp; aggregates, B/E 
                   
               
               
                 Dry IPE 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 B + peaks 
               
               
                   
                 2) positive pressure  
                 2) off-white solids 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                 MTBE 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 B + peaks 
               
               
                   
                 2) positive pressure  
                 2) off-white solids 
                   
               
               
                   
                 filtration 
                   
                   
               
               
                 Dry NMP 
                 1) slurry, RT, 10 d 
                 1) orange slurry 
                 F (analyzed 
               
               
                   
                 2) positive pressure  
                 2) off-white solids; fine  
                 damp) c   
               
               
                   
                 filtration 
                 &amp; aggregates, B/E 
                   
               
               
                 TAME 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 B + minor 
               
               
                   
                 2) positive pressure  
                 2) off-white solids 
                 peaks 
               
               
                   
                 filtration 
                   
                   
               
               
                 80:20 
                 1) slurry, RT, 10 d 
                 1) off-white slurry 
                 A + peaks 
               
               
                 TFE/H 2 O 
                 2) positive pressure  
                 2) off-white solids; fine  
                 (disordered) 
               
               
                 (a w  = 1.00) 
                 filtration 
                 &amp; aggregates, partial B/E 
                   
               
               
                 99:1 
                 1) slurry, RT, 11 d 
                 1) pale orange slurry 
                 L (analyzed 
               
               
                 THF/H 2 O 
                 2) centrifuge &amp;  
                 2) damp off-white solids; 
                 damp) 
               
               
                 (a w  = 0.21) 
                 decant 
                 fines, B/E 
                   
               
               
                 97:3 
                 1) slurry, RT, 11 d 
                 1) yellow slurry 
                 M (analyzed 
               
               
                 THF/H 2 O 
                 2) centrifuge &amp;  
                 2) damp off-white solids; 
                 damp) 
               
               
                 (a w  = 0.53) 
                 decant 
                 fines, B/E 
                   
               
               
                 93:7 
                 1) slurry, RT, 11 d 
                 1) yellow slurry 
                 L + peaks 
               
               
                 THF/H 2 O 
                 2) centrifuge &amp;  
                 2) damp off-white solids; 
                 (analyzed 
               
               
                 (a w  = 0.91) 
                 decant 
                 fines, B/E 
                 damp) 
               
               
                   
               
               
                   a Solvent ratios are v/v. 
               
               
                   b Temperatures and times are approximate. 
               
               
                   c Sample 1 in Table 25. 
               
               
                   d Sample 3 in Table 25. 
               
               
                   e Sample 4 in Table 25. 
               
               
                   f Sample 5 in Table 25. 
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 24 
               
               
                   
               
               
                 Solvent a   
                 Conditions b   
                 Observations 
                 XRPD Results 
               
               
                   
               
             
            
               
                 — 
                 P 2 O 5  jar, 0% RH RT, 12 d 
                 White solids 
                 B + peaks 
               
               
                   
                   
                   
                 (slight 
               
               
                   
                   
                   
                 disorder) 
               
               
                 — 
                 23% RH, RT, 6 d 
                 White solids 
                 B + minor A 
               
               
                 — 
                 43% RH, RT, 6 d 
                 White solids 
                 A + B 
               
               
                 — 
                 54% RH, RT, 6 d 
                 White solids 
                 A + B 
               
               
                 Dry CPME 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 A + minor N 
               
               
                   
                 2) positive pressure filtration 
                 2) off-white solids 
                   
               
               
                   
                 3) 90% RH, RT, 10 d 
                 3) off-white solids 
                   
               
               
                 EtOH 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 Disordered 
               
               
                   
                 2) positive pressure filtration 
                 2) off-white solids 
                 mixture of 
               
               
                   
                 3) 90% RH, RT, 10 d 
                 3) off-white solids 
                 peaks 
               
               
                 Dry IPE 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 A (shifted) + 
               
               
                   
                 2) positive pressure filtration 
                 2) off-white solids 
                 minor B + 
               
               
                   
                 3) 90% RH, RT, 10 d 
                 3) off-white solids 
                 peaks 
               
               
                 MTBE 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 A (shifted) + 
               
               
                   
                 2) positive pressure filtration 
                 2) off-white solids 
                 minor B + 
               
               
                   
                 3) 90% RH, RT, 10 d 
                 3) off-white solids 
                 peaks 
               
               
                 Dry HFIPA 
                 FE 
                 Orange solids; long, 
                 J 
               
               
                   
                   
                 dendritic needles &amp; 
                   
               
               
                   
                   
                 aggregates, B/E 
                   
               
               
                 TAME 
                 1) slurry, 50° C., 7 d 
                 1) pale yellow slurry 
                 A + minor B + 
               
               
                   
                 2) positive pressure filtration 
                 2) off-white solids 
                 minor peaks 
               
               
                   
                 3) 90% RH, RT, 10 d 
                 3) off-white solids 
                   
               
               
                 Dry TFE 
                 FE 
                 Pale orange solids; dendritic 
                 K 
               
               
                   
                   
                 needles &amp; aggregates, B/E 
                   
               
               
                 Dry THF 
                 SC (55° C. to RT) 
                 Tablets in clear soln; B/E- 
                 L + minor B 
               
               
                   
                   
                 potential singles 
               
               
                   
               
               
                   a Solvent ratios are v/v. 
               
               
                   b Temperatures and times are approximate. 
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 25 
               
               
                   
               
               
                 Starting Material 
                 Condition 
                 XRPD Result 
               
               
                   
               
             
            
               
                 Form D (Sample 1) 
                 vac., RT, 1 d 
                 Form D a   
               
               
                 Form D (Sample 2) 
                 vac., 80° C., 1 d 
                 Form D + peaks (some disorder) 
               
               
                 Form E (Sample 3) 
                 vac., RT, 1 d 
                 Form H (some disorder) 
               
               
                 Form F (Sample 4) 
                 vac., RT, 1 d 
                 Form F 
               
               
                 Form G (Sample 5) 
                 vac., RT, 1 d 
                 Form B + peaks (some disorder) 
               
               
                   
               
               
                   a Sample 2. 
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 26 
               
               
                   
               
               
                   
                 Analytical 
                   
               
               
                 Form 
                 Technique 
                 Results 
               
               
                   
               
             
            
               
                 A 
                 XRPD 
                 Consistent w/indexing solution; has slight solvent halo 
               
               
                   
                   1 H NMR 
                 Consistent w/chemical structure; no apparent organic 
               
               
                   
                   
                 solvent 
               
               
                   
                 TGA/ 
                 9.3% wt loss over 41 to 136° C. (equivalent to 2.8  
               
               
                   
                 DSC a   
                 mol/mol H 2 O) (TGA); large broad endo at 117.9° C.  
               
               
                   
                   
                 and sharper endo at 307.8° C. (DSC) 
               
               
                   
                 VRH- 
                 Form A-initial scan; equilibrated ~45 min at ~30% RH 
               
               
                   
                 XRPD 
                 variable RH patterns (10 min. scans) 
               
               
                   
                   
                 Form B-initial scan after equilibrating under N2 stream  
               
               
                   
                   
                 (~0% RH) 17 h 
               
               
                   
                   
                 variable RH patterns (10 min. scans) 
               
               
                 B 
                 XRPD 
                 consistent w/indexing solution from VRH-XRPD 
               
               
                   
                   
                 experiments, with additional minor 
               
               
                   
                   
                 peaks 
               
               
                   
                   1 H NMR 
                 Consistent w/chemical structure; negligible amount of 
               
               
                   
                   
                 TAME 
               
               
                   
                 TGA/ 
                 0.1% wt loss over 50 to 121° C. and 0.2% wt loss over  
               
               
                   
                 DSC a   
                 229 to 267° C.; decomp, onset at 334° C. (TGA); 2  
               
               
                   
                   
                 overlapping endos w/peak at 307.8° C. (DSC) 
               
               
                 C 
                 XRPD 
                 successfully indexed; unit cell capable of containing up  
               
               
                   
                   
                 to 3 acetic acid molecules 
               
               
                   
                   1 H NMR 
                 consistent w/chemical structure, 2.9 mol/mol AcOH 
               
               
                   
                 TGA/ 
                 16.6% wt loss over 71 to 137° C. (equivalent to 1.7  
               
               
                   
                 DSC a   
                 mol/mol AcOH) and 8.0% wt loss over 171 to 203° C.  
               
               
                   
                   
                 (equivalent to 0.7 mol/mol AcOH) (TGA); Endotherms  
               
               
                   
                   
                 at 102.8° C., 190.1° C., &amp; 308.4° C. (DSC) 
               
               
                 D 
                 XRPD 
                 successfully indexed as di-DMA solvate; isostructural  
               
               
                   
                   
                 with Form F 
               
               
                   
                   1 H NMR 
                 consistent with chemical structure; 1.7 mol/mol DMA  
               
               
                   
                   
                 &amp; 0.2 mol/mol NMP b   
               
               
                   
                 TGA/ 
                 25.5% wt loss over 101 to 186° C. (equivalent to  
               
               
                   
                 DSC a   
                 1.9 mol/mol DMA) (TGA); sharp endotherms at  
               
               
                   
                   
                 117.7° C. and 305.4° C. (DSC) 
               
               
                 E 
                 XRPD 
                 successfully indexed; unit cell capable of containing  
               
               
                   
                   
                 2-3 DMSO molecules 
               
               
                 F 
                 XRPD 
                 successfully indexed as di-NMP solvate; isostructural  
               
               
                   
                   
                 with Form D 
               
               
                   
                   1 H NMR 
                 consistent with chemical structure; equivalent to  
               
               
                   
                   
                 1.7 mol/mol NMP &amp; 0.2 mol/mol DMA b   
               
               
                   
                 TGA/ 
                 27.5% wt loss over 104 to 233° C. (equivalent to  
               
               
                   
                 DSCA 
                 1.9 mol/mol NMP) (TGA); sharp endotherms at  
               
               
                   
                   
                 126.5° C. and 305.4° C. (DSC)  
               
               
                 G 
                 XRPD 
                 successfully indexed; unit cell capable of containing  
               
               
                   
                   
                 up to 2 DMF molecules 
               
               
                 H 
                 XRPD 
                 Not indexable 
               
               
                 J 
                 XRPD 
                 Not indexable 
               
               
                 K 
                 XRPD 
                 Not indexable 
               
               
                 L 
                 XRPD 
                 successfully indexed; unit cell capable of containing  
               
               
                   
                   
                 up to 2 THF molecules 
               
               
                 M 
                 XRPD 
                 successfully indexed; unit cell capable of containing  
               
               
                   
                   
                 2-3 THF molecules 
               
               
                 N 
                 XRPD 
                 successfully indexed as anhydrous material 
               
               
                   
                   1 H NMR 
                 consistent w/chemical structure; negligible amount  
               
               
                   
                   
                 of CPME  
               
               
                   
                 TGA/ 
                 0.1% wt loss over 50 to 120° C. and 0.2%  
               
               
                   
                 DSC a   
                 wt loss over 209 to 252° C.; decomp, onset at  
               
               
                   
                   
                 336° C. (TGA); two overlapping endotherms with  
               
               
                   
                   
                 peak at 307.2° C. (DSC) 
               
               
                 P 
                 XRPD 
                 successfully indexed with a few minor peaks that are  
               
               
                   
                   
                 not included in indexing solution, space for 1-2  
               
               
                   
                   
                 EtOAc molecules 
               
               
                   
               
               
                   a Weight changes (%) in TGA are rounded to 1 decimal place; temperatures are rounded to nearest degree. Temperatures in DSC are rounded to 1 decimal place. 
               
               
                   b Samples were under vacuum in same oven as each other, allowing solvent to swap between isostructural solvates. 
               
            
           
         
       
     
       FIG.  18 A ,  FIG.  18 B , and  FIG.  18 C  provide a summary of the XRPD spectra for various Forms identified. 
       FIG.  43    provides a schematic representation of certain results obtained from these polymorph screening experiments. 
     Example 11: Compound 1 Form A 
     An exemplary procedure for preparing Compound 1 Form A is as follows: Compound 1 Lot II (459.1 mg) was slurried in THF (4 mL). Concentrated HCl (154 μL, 2 equiv.) was added to the slurry. The off-white slurry rapidly changed to a yellow slurry. The slurry was stirred at ambient temperature for 1 day. Solids were collected by vacuum filtration and briefly dried under vacuum. The yellow material, assumed to be an HCl salt, was collected by vacuum filtration. The material (543.2 mg) was then suspended in H 2 O (5 mL) and stirred at ambient temperature for 2 days. Pale yellow solids were collected by vacuum filtration but appeared to still contain some HCl salt by XRPD. Solids were re-slurried in H 2 O (1 mL) at ambient temperature for additional 3 days. The off-white solids were collected by vacuum filtration and dried on filter until solids were no longer visibly damp. 
     Solution  1 H NMR for Form A was consistent with the chemical structure and contained no apparent organic solvent. 
       FIG.  19    provides an XRPD spectrum of Compound 1 Form A. 
       FIG.  20    provides a TGA/DSC curve of Compound 1 Form A. Thermal characterization by TGA provided a 9.3% weight loss from 41 to 136° C. which was calculated to be equivalent to ˜2.8 mol/mol H 2 O. DSC displayed a large broad endotherm at 117.9° C. and a slightly sharper endotherm at 307.8° C. 
     Example 12: Compound 1 Form B 
     Form B was observed in Compound 1 Lots I, II, and III. Additionally, Form B was prepared by slurrying Compound 1 (approx. 50 mg) in tert-amyl methyl ether (TAME) at 50° C. for 7 days. The solids were isolated by filtration and analyzed. An XRPD spectrum of the sample contained a few additional minor peaks, and  1 H NMR was consistent with the chemical structure of Compound 1. A negligible amount of TAME was also present in the sample. 
     Thermal characterization by TGA and DSC was also obtained ( FIG.  21   ). Only a 0.1% weight loss was observed from 50° C. to 121° C. with an additional 0.2% weight loss over 229-267° C. range. The onset of decomposition appeared to occur at approximately 334° C. The DSC thermogram displayed two overlapping endotherms with the sharpest peak at 307.8° C. 
       FIG.  22    provides an XRPD spectrum of Compound 1 Form B, obtained at low relative humidity (RH) during a variable relative humidity experiment of Example 24. Indexing of this spectrum suggested a unit cell volume consistent with an anhydrous form. 
     Example 13: Compound 1 Form C 
     Form C was prepared by slurring Compound 1 (approx. 50 mg) in acetic acid at ambient temperature for 10 days. The solids were isolated by filtration and analyzed. 
     XRPD analysis indicated a unit cell capable of containing up to 3 acetic acid molecules ( FIG.  23   ). The proton NMR spectrum obtained for this sample was consistent with Compound 1 containing ˜2.9 mol/mol AcOH. 
     Thermal characterization by TGA provided a thermogram with a two-step weight loss ( FIG.  24   ). A 16.6% weight loss, equivalent to ˜1.7 mol/mol AcOH, was observed from 71° C. to 137° C. followed by an 8% weight loss, equivalent to ˜0.7 mol/mol AcOH, from 171° C. to 203° C. The DSC thermogram displayed endotherms that coincided with the TGA events with peaks at 102.8° C., 190.1° C. and 308.4° C. 
     Form C was assigned as a tri-acetic acid cocrystal. 
     Example 14: Compound 1 Form D 
     Form D was prepared by slurrying Compound 1 (approx. 50 mg) in DMA at ambient temperature for 10 days. The solids were isolated by filtration and analyzed. 
     XRPD analysis of the slightly damp material indicated a unit cell consistent with a di-DMA solvate ( FIG.  25   ). This XRPD pattern also appeared to be isostructural with NMP-solvated material, Form F. 
     Before further characterization was completed, the damp solids were dried in a vacuum oven with other damp materials, including Form F produced in NMP. Proton NMR spectroscopy data was consistent with chemical structure of Compound 1 and showed ˜1.7 mol/mol DMA. In addition, a small amount of NMP appeared to be present (0.2 mol/mol NMP). This was likely due to a solvent exchange that occurred during vacuum drying. 
     The TGA thermogram displayed a 25.5% weight loss over 101° C. to 186° C. ( FIG.  26   ), equivalent to ˜1.9 mol/mol DMA. The weight loss coincided with an endotherm at 117.7° C. in the DSC thermogram. A sharp endotherm was also observed at 305.4° C. 
     Example 15: Compound 1 Form E and Compound 1 Form H 
     Form E was prepared by slurrying Compound 1 (approx. 50 mg) in DMSO at ambient temperature for 10 days. The solids were isolated by filtration and analyzed. 
     XRPD analysis of the damp solids indicated a unit cell capable of containing up to 3 DMSO molecules ( FIG.  27   ). 
     The sample was then dried in an ambient temperature vacuum oven. After 1 day, a new XRPD pattern was observed and designated Form H ( FIG.  28   ). 
     Example 16: Compound 1 Form F 
     Form F was prepared by slurrying Compound 1 (approx. 50 mg) in NMP at ambient temperature for 10 days. The solids were isolated by filtration and analyzed. 
     XRPD analysis of the slightly damp material indicated a unit cell consistent with a di-NMP solvate of Compound 1 ( FIG.  29   ). This XRPD pattern was similar to the pattern of Form D, which suggested that the two forms are isostructural. 
     Before further characterization was conducted, the damp solids were dried in a vacuum oven with other damp materials, including Form D. Proton NMR spectroscopy was consistent with chemical structure of Compound 1 and contained ˜1.7 mol/mol NMP. In addition, a small amount of DMA appeared to be present (˜0.2 mol/mol DMA). This was likely due to a solvent exchange that occurred during vacuum drying. 
     Thermal characterization by TGA displayed a 27.5% weight loss over 104° C. to 233° C., which is consistent with a loss of ˜1.9 mol/mol NMP ( FIG.  30   ). The DSC thermogram displayed an endotherm at 126.5° C., which is consistent with the weight loss in the TGA. An additional sharp endotherm was observed at 305.4° C. 
     Example 17: Compound 1 Form G 
     Form G was prepared by slurrying Compound 1 (approx. 50 mg) in DMF at ambient temperature for 10 days. The solids were isolated by filtration and analyzed. 
     XRPD analysis of the slightly damp material indicated a unit cell capable of containing up to 2 molecules of DMF ( FIG.  31   ). Upon vacuum drying, the sample desolvated to give Form B. 
     Example 18: Compound 1 Form J and Compound 1 Form K 
     Form J and Form K were prepared by fast evaporation from hexafluoroisopropanol (HFIPA) and trifluoroethanol (TFE), respectively: A solution of Compound 1 was prepared in dry HFIPA or dry TFE. The solution was filtered with a 0.2 μm PTFE syringe filter and left open at ambient conditions until there was no apparent solvent. Dry solids were analyzed by XRPD. 
       FIG.  32    provides an XRPD pattern of Form J, and  FIG.  33    provides an XRPD pattern of Form K, obtained from these experiments. 
     Example 19: Compound 1 Form L 
     Form L was prepared by slurrying Compound 1 (approx. 50 mg) in THF/H 2 O (99:1) at ambient temperature for 11 days. The solids were isolated by centrifugation and decantation, then analyzed. 
     XRPD analysis indicated a unit cell capable of containing up to 2 molecules of THF ( FIG.  34   ). 
     Example 20: Compound 1 Form M 
     Form M was prepared by slurrying Compound 1 (approx. 50 mg) in THF/H 2 O (97:3) at ambient temperature for 11 days. The solids were isolated by centrifugation and decantation, then analyzed. 
     XRPD analysis indicated a unit cell capable of containing 2-3 molecules of THE ( FIG.  35   ). 
     Example 21: Compound 1 Form N 
     An exemplary procedure for preparing Compound 1 Form N is as follows: Compound 1 Lot II (61.0 mg) was slurried in dry cyclopentyl methyl ether (CPME) (2 mL) at 50° C. for 7 days. Pale yellow solids were collected by positive pressure filtration on a 0.2 μm nylon filter. The solids were stored in a clean vial over Drierite until XRPD analysis was performed. 
     Solution  1 H NMR of Form N was consistent with the chemical structure of Compound 1 and contained less than ˜0.1 mol/mol CPME. 
       FIG.  36    provides an XRPD spectrum of Compound 1 Form N. XRPD analysis indicated a unit cell smaller than that observed for Form B. 
     The TGA thermogram displayed a 0.1% weight loss over 50° C. to 120° C. and a 0.2% weight loss over 209° C. to 252° C. ( FIG.  37   ). Decomposition appears to have an onset at 336° C. The DSC thermogram displayed two overlapping endotherms with a peak at 307.2° C. 
     Form N was assigned as an anhydrous form. 
     Example 22: Compound 1 Form P 
     Form P was prepared by slurrying Compound 1 (approx. 50 mg) in ethyl acetate at ambient temperature for 3 days. The solids were isolated by filtration and analyzed. 
     XRPD analysis indicated a unit cell capable of containing 1-2 ethyl acetate molecules ( FIG.  38   ). 
     Example 23: Variable Relative Humidity (VRH) Experiments 
     VRH-XRPD analysis was conducted to help determine water activity boundary for the solid-state conversion between hydrated Form A and anhydrous Form B. This method was utilized due the observed high tendency of Compound 1 to form solvates, which precluded the use of solvent-mediated approach. 
     Overall, two VRH-XRPD experiments were conducted to qualitatively evaluate RH conditions leading to predominance of Form A over Form B and vice versa. The kinetic component was not assessed. 
     Experiment 1 
     The first VRH-XRPD experiment was conducted with a goal of observing dehydration of hydrated Form A. An initial XRPD scan was, therefore, acquired on Form A equilibrated in-situ at ambient RH for 45 minutes, which at the time of the analysis was ˜30%. The XRPD pattern from this scan was consistent with Form A ( FIG.  39   , top). 
     The RH level was increased to ˜85% RH over 2.5 hours and after that, incrementally decreased while holding at each RH level for 1-2 hours. XRPD patterns were collected throughout the course of the experiment, each with a 10 minute scan. 
     Only Form A and Form B were observed in the experiment. The XRPD patterns were consistently Form A throughout the increase and decrease of the RH until the RH was lowered to approximately 21% RH, at which point a small amount of Form B became visible ( FIG.  39   , second from top). The amount of Form B remained unchanged until the RH was lowered to ˜15% RH, where more Form B was observed. At 11% RH, Form B became the predominant phase in the mixture. As the RH level continued to drop, more Form B and less Form A was present from 15% to 7% RH ( FIG.  39   , middle two spectra). By the time the RH reached ˜5% RH, Form A was no longer visible in the patterns ( FIG.  39   , bottom two spectra). 
     Experiment 2 
     The focus of the second VRH-XRPD experiment was to observe transformation of anhydrous Form B. For this purpose, the starting Form A was converted to Form B in-situ by an overnight hold under nitrogen stream (˜0% RH) ( FIG.  40   ). 
     The RH was then incrementally increased with long holds at each step (15% up to ˜60%). XRPD patterns were collected throughout the course of the experiment, each with a 10 minute scan. The XRPD patterns remained Form B until the RH reached approximately 60% RH, where Form A became the primary phase with some Form B remaining ( FIG.  41   , top two spectra). Further decrease of Form B was observed through the remainder of the 60% RH hold at which point the experiment ended ( FIG.  41   , bottom two spectra). Complete conversion to Form A from Form B was not observed under these conditions. 
     A schematic presentation of both VRH-XRPD experiments is provided in  FIG.  42    where Form A/Form B ratios were plotted versus average RH values. The ratios were estimated for illustration purposes only and do not provide quantitative assessment of Form A and Form B contents. Intensities of selected XRPD peaks were used for ratios estimations and specificity, preferred orientation, etc. were not evaluated. 
     The plotted VRH-XRPD data were compared with water uptakes seen for Compound 1 Lot I during its DVS analysis ( FIG.  2   ). 
     Overall, VRH-XRPD and DVS data were in good agreement, indicating that anhydrous Form B likely exists below 20% RH but may be kinetically stable at up to 40-60% RH. Hydrated Form A will expect to begin dehydration at 20% RH and fully convert to anhydrous Form B at zero RH. 
     While we have described a number of embodiments of this disclosure, it is apparent that our basic examples may be altered to provide other embodiments that utilize the compounds and methods of this disclosure. Therefore, it will be appreciated that the scope of this disclosure is to be defined by the appended claims rather than by the specific embodiments that have been represented by way of example.