Patent Publication Number: US-2011053997-A1

Title: Salts and Crystal Forms

Description:
This invention relates to salts of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, polymorphs of the salts and methods of their preparation. 
     (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihythoimidazole-2-thione hydrochloride (the compound of formula I, below) is a potent, non-toxic and peripherally selective inhibitor of DβM, which can be used for treatment of certain cardiovascular disorders. It is disclosed in WO2004/033447, along with processes for its preparation. 
     
       
         
         
             
             
         
       
     
     The process disclosed in WO2004/033447 for preparing compound 1 (see example 16) results in the amorphous form of compound 1. The process of example 16 is described in WO2004/033447 on page 5, lines 16 to 21 and in Scheme 2 on page 7. Prior to formation of compound 1, a mixture of intermediates is formed (compounds V and VI in scheme 2). The mixture of intermediates is subjected to a high concentration of HCl in ethyl acetate. Under these conditions, the primary product of the reaction is compound I, which precipitates as it forms as the amorphous form. 
     WO2007/139413 discloses polymorphic forms of compound 1. 
     The compounds disclosed in WO2004/033447 may exhibit advantageous properties. The polymorphs disclosed in WO2007/139413 may also exhibit advantageous properties. For example, the products may be advantageous in terms of their ease of production, for example easier filterability or drying. The products may be easy to store. The products may have increased processability. The products may be produced in high yield and/or high purity. The products may be advantageous in terms of their physical characteristics, such as solubility, melting point, hardness, density, hygroscopicity, stability, compatibility with excipients when formulated as a pharmaceutical. Furthermore, the products may have physiological advantages, for example they may exhibit high bioavailability. 
     We have now found certain new and advantageous salts of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione and new and advantageous polymorphs thereof. 
     Accordingly, the present invention provides salts of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, other than the hydrochloride salt, and crystalline polymorphs of the salts. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione has the following structure and is hereinafter referred to as compound 2. 
     
       
         
         
             
             
         
       
     
     The present invention provides salts of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione other than the hydrochloride salt. In particular, the present invention provides the following acid addition salts of compound 2: L-tartaric, malonic, toluenesulfonic, camphorsulfonic, fumaric, acetic, adipic, glutaric, glycolic, L-malic, citric, gentisic, maleic, hydrobromide, succinic, phosphoric and sulfuric. Each of the salts was found to exist in at least one crystalline polymorphic form and the present invention provides the characterisation of each of the forms. 
     Unless otherwise stated, all peak positions expressed in units of °2θ are subject to a margin of ±0.2 °2θ. 
     In the following description of the present invention, the polymorphic forms are described as having an XRPD pattern with peaks at the positions listed in the respective Tables. It is to be understood that, in one embodiment, the polymorphic form has an XRPD pattern with peaks at the °2θ positions listed±0.2 °2θ with any intensity (% (I/Io)) value; or in another embodiment, an XRPD pattern with peaks at the °2θ positions listed±0.1 °2θ. It is to be noted that the intensity values are included for information only and the definition of each of the peaks is not to be construed as being limited to particular intensity values. 
     According to one aspect of the present invention, there is provided the L-tartaric acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate. 
     In an embodiment, there is provided (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate in amorphous form. 
     In an embodiment, the amorphous form of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate has an XRPD as shown in  FIG. 1   a.    
     In another embodiment, there is provided crystalline Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate. 
     Form A may be characterised as having an XRPD pattern with peaks at 4.7, 6.0, 10.5, 11.5 and 14.0 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 16.4, 17.6 and 19.1 °2θ±0.2 °2θ. Form A may be characterised as having an absence of XRPD peaks between 6.5 and 10.0 °2θ. 
     In an embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 1 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.7 ± 0.1 
                 18.842 ± 0.410  
                 54 
               
               
                  6.0 ± 0.1 
                 14.780 ± 0.251  
                 27 
               
               
                 10.5 ± 0.1 
                 8.417 ± 0.081 
                 45 
               
               
                 11.5 ± 0.1 
                 7.715 ± 0.068 
                 79 
               
               
                 14.0 ± 0.1 
                 6.317 ± 0.045 
                 34 
               
               
                 16.4 ± 0.1 
                 5.389 ± 0.033 
                 35 
               
               
                 17.6 ± 0.1 
                 5.034 ± 0.029 
                 100 
               
               
                 19.1 ± 0.1 
                 4.649 ± 0.024 
                 69 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 2 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                   
                   
                 Intensity 
               
               
                 ° 2θ 
                 d space (Å) 
                 % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.7 ± 0.1 
                 18.842 ± 0.410  
                 54 
               
               
                  6.0 ± 0.1 
                 14.780 ± 0.251  
                 27 
               
               
                 10.5 ± 0.1 
                 8.417 ± 0.081 
                 45 
               
               
                 11.5 ± 0.1 
                 7.715 ± 0.068 
                 79 
               
               
                 14.0 ± 0.1 
                 6.317 ± 0.045 
                 34 
               
               
                 14.4 ± 0.1 
                 6.160 ± 0.043 
                 34 
               
               
                 14.8 ± 0.1 
                 5.998 ± 0.041 
                 62 
               
               
                 16.4 ± 0.1 
                 5.389 ± 0.033 
                 35 
               
               
                 17.1 ± 0.1 
                 5.173 ± 0.030 
                 66 
               
               
                 17.6 ± 0.1 
                 5.034 ± 0.029 
                 100 
               
               
                 19.1 ± 0.1 
                 4.649 ± 0.024 
                 69 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 3 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity(%) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.7 ± 0.1 
                 18.842 ± 0.410  
                 54 
               
               
                  6.0 ± 0.1 
                 14.780 ± 0.251  
                 27 
               
               
                 10.5 ± 0.1 
                 8.417 ± 0.081 
                 45 
               
               
                 11.5 ± 0.1 
                 7.715 ± 0.068 
                 79 
               
               
                 11.9 ± 0.1 
                 7.425 ± 0.063 
                 26 
               
               
                 12.6 ± 0.1 
                 7.003 ± 0.056 
                 15 
               
               
                 13.2 ± 0.1 
                 6.718 ± 0.051 
                 13 
               
               
                 14.0 ± 0.1 
                 6.317 ± 0.045 
                 34 
               
               
                 14.4 ± 0.1 
                 6.160 ± 0.043 
                 34 
               
               
                 14.8 ± 0.1 
                 5.998 ± 0.041 
                 62 
               
               
                 15.2 ± 0.1 
                 5.844 ± 0.039 
                 50 
               
               
                 16.4 ± 0.1 
                 5.389 ± 0.033 
                 35 
               
               
                 17.1 ± 0.1 
                 5.173 ± 0.030 
                 66 
               
               
                 17.6 ± 0.1 
                 5.034 ± 0.029 
                 100 
               
               
                 18.1 ± 0.1 
                 4.901 ± 0.027 
                 30 
               
               
                 19.1 ± 0.1 
                 4.649 ± 0.024 
                 69 
               
               
                 19.8 ± 0.1 
                 4.482 ± 0.023 
                 54 
               
               
                 20.0 ± 0.1 
                 4.442 ± 0.022 
                 49 
               
               
                 20.9 ± 0.1 
                 4.259 ± 0.020 
                 36 
               
               
                 21.2 ± 0.1 
                 4.193 ± 0.020 
                 61 
               
               
                 21.9 ± 0.1 
                 4.057 ± 0.018 
                 31 
               
               
                 22.8 ± 0.1 
                 3.894 ± 0.017 
                 38 
               
               
                 24.1 ± 0.1 
                 3.693 ± 0.015 
                 77 
               
               
                 24.8 ± 0.1 
                 3.592 ± 0.014 
                 51 
               
               
                 25.7 ± 0.1 
                 3.468 ± 0.013 
                 27 
               
               
                 26.5 ± 0.1 
                 3.360 ± 0.012 
                 33 
               
               
                 27.1 ± 0.1 
                 3.290 ± 0.012 
                 28 
               
               
                 28.2 ± 0.1 
                 3.160 ± 0.011 
                 38 
               
               
                 28.8 ± 0.1 
                 3.099 ± 0.011 
                 28 
               
               
                 29.6 ± 0.1 
                 3.013 ± 0.010 
                 38 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate has the XRPD pattern as shown in  FIG. 3   a.    
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate has the XRPD pattern as shown in  FIG. 71 . 
     In another embodiment, there is provided crystalline Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate. 
     Form B may be characterised as having an XRPD pattern with peaks at 5.4, 9.0 and 13.7 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 16.7 and 20.6 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 11.7, 13.1 and 14.9 °2θ±0.2°θ. 
     In an embodiment, Form B has an XRPD pattern with peaks at the positions listed in Table 4 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.4 ± 0.1 
                 16.519 ± 0.314  
                 100 
               
               
                  9.0 ± 0.1 
                 9.881 ± 0.111 
                 57 
               
               
                 13.7 ± 0.1 
                 6.468 ± 0.047 
                 40 
               
               
                 16.7 ± 0.1 
                 5.312 ± 0.032 
                 41 
               
               
                 20.6 ± 0.1 
                 4.320 ± 0.021 
                 71 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form B has an XRPD pattern with peaks at the positions listed in Table 5 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.4 ± 0.1 
                 16.519 ± 0.314  
                 100 
               
               
                  9.0 ± 0.1 
                 9.881 ± 0.111 
                 57 
               
               
                 11.7 ± 0.1 
                 7.557 ± 0.065 
                 42 
               
               
                 13.1 ± 0.1 
                 6.764 ± 0.052 
                 94 
               
               
                 13.7 ± 0.1 
                 6.468 ± 0.047 
                 40 
               
               
                 14.9 ± 0.1 
                 5.950 ± 0.040 
                 54 
               
               
                 16.7 ± 0.1 
                 5.312 ± 0.032 
                 41 
               
               
                 17.8 ± 0.1 
                 4.983 ± 0.028 
                 58 
               
               
                 18.1 ± 0.1 
                 4.893 ± 0.027 
                 75 
               
               
                 19.8 ± 0.1 
                 4.482 ± 0.023 
                 39 
               
               
                 20.6 ± 0.1 
                 4.320 ± 0.021 
                 71 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form B has an XRPD pattern with peaks at the positions listed in Table 6 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.4 ± 0.1 
                 16.519 ± 0.314  
                 100 
               
               
                  9.0 ± 0.1 
                 9.881 ± 0.111 
                 57 
               
               
                 11.7 ± 0.1 
                 7.557 ± 0.065 
                 42 
               
               
                 13.1 ± 0.1 
                 6.764 ± 0.052 
                 94 
               
               
                 13.7 ± 0.1 
                 6.468 ± 0.047 
                 40 
               
               
                 14.9 ± 0.1 
                 5.950 ± 0.040 
                 54 
               
               
                 16.7 ± 0.1 
                 5.312 ± 0.032 
                 41 
               
               
                 17.2 ± 0.1 
                 5.147 ± 0.030 
                 34 
               
               
                 17.8 ± 0.1 
                 4.983 ± 0.028 
                 58 
               
               
                 18.1 ± 0.1 
                 4.893 ± 0.027 
                 75 
               
               
                 19.8 ± 0.1 
                 4.482 ± 0.023 
                 39 
               
               
                 20.6 ± 0.1 
                 4.320 ± 0.021 
                 71 
               
               
                 21.5 ± 0.1 
                 4.135 ± 0.019 
                 49 
               
               
                 22.3 ± 0.1 
                 3.981 ± 0.018 
                 39 
               
               
                 23.1 ± 0.1 
                 3.854 ± 0.017 
                 43 
               
               
                 23.4 ± 0.1 
                 3.800 ± 0.016 
                 62 
               
               
                 24.0 ± 0.1 
                 3.716 ± 0.015 
                 69 
               
               
                 24.5 ± 0.1 
                 3.631 ± 0.015 
                 45 
               
               
                 26.6 ± 0.1 
                 3.356 ± 0.012 
                 40 
               
               
                 29.5 ± 0.1 
                 3.031 ± 0.010 
                 44 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate has the XRPD pattern as shown in  FIG. 3   b . In an embodiment, Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate has the XRPD pattern as shown in  FIG. 72 . 
     In another embodiment, Form B is characterised as being in the form of a solvate of tetrahydrofuran (THF). The number of moles of tetrahydrofuran per mole of Form B may range from 0.4 to 0.9. Typically, the number of moles ranges from 0.5 to 0.8. In an embodiment, there is 0.7 mole of THF per 1 mole of Form B. 
     According to another aspect of the present invention, there is provided the malonic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malonate. 
     In an embodiment, there is provided crystalline Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malonate. 
     Form A may be characterised as having an XRPD pattern with peaks at 5.2, 12.1, 13.0, 13.6, 14.1 and 14.8 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 15.7 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 19.2 and 20.4 °2θ±0.2°θ. 
     In an embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 7 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.2 ± 0.1 
                 16.897 ± 0.329  
                 15 
               
               
                 12.1 ± 0.1 
                 7.297 ± 0.060 
                 32 
               
               
                 13.0 ± 0.1 
                 6.795 ± 0.052 
                 28 
               
               
                 13.6 ± 0.1 
                 6.511 ± 0.048 
                 44 
               
               
                 14.1 ± 0.1 
                 6.290 ± 0.045 
                 58 
               
               
                 14.8 ± 0.1 
                 5.998 ± 0.041 
                 28 
               
               
                 15.7 ± 0.1 
                 5.645 ± 0.036 
                 100 
               
               
                 19.2 ± 0.1 
                 4.628 ± 0.024 
                 27 
               
               
                 20.4 ± 0.1 
                 4.364 ± 0.021 
                 30 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form B has an XRPD pattern with peaks at the positions listed in Table 8 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 8 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.2 ± 0.1 
                 16.897 ± 0.329  
                 15 
               
               
                 10.5 ± 0.1 
                 8.441 ± 0.081 
                 4 
               
               
                 11.5 ± 0.1 
                 7.695 ± 0.067 
                 4 
               
               
                 12.1 ± 0.1 
                 7.297 ± 0.060 
                 32 
               
               
                 13.0 ± 0.1 
                 6.795 ± 0.052 
                 28 
               
               
                 13.6 ± 0.1 
                 6.511 ± 0.048 
                 44 
               
               
                 14.1 ± 0.1 
                 6.290 ± 0.045 
                 58 
               
               
                 14.8 ± 0.1 
                 5.998 ± 0.041 
                 28 
               
               
                 15.7 ± 0.1 
                 5.645 ± 0.036 
                 100 
               
               
                 16.2 ± 0.1 
                 5.478 ± 0.034 
                 12 
               
               
                 17.9 ± 0.1 
                 4.958 ± 0.028 
                 9 
               
               
                 19.2 ± 0.1 
                 4.628 ± 0.024 
                 27 
               
               
                 20.4 ± 0.1 
                 4.364 ± 0.021 
                 30 
               
               
                 20.9 ± 0.1 
                 4.246 ± 0.020 
                 26 
               
               
                 21.2 ± 0.1 
                 4.193 ± 0.020 
                 15 
               
               
                 22.7 ± 0.1 
                 3.919 ± 0.017 
                 40 
               
               
                 22.9 ± 0.1 
                 3.879 ± 0.017 
                 70 
               
               
                 24.0 ± 0.1 
                 3.702 ± 0.015 
                 54 
               
               
                 24.6 ± 0.1 
                 3.626 ± 0.015 
                 14 
               
               
                 24.9 ± 0.1 
                 3.570 ± 0.014 
                 44 
               
               
                 25.4 ± 0.1 
                 3.500 ± 0.014 
                 7 
               
               
                 26.2 ± 0.1 
                 3.398 ± 0.013 
                 34 
               
               
                 27.0 ± 0.1 
                 3.298 ± 0.012 
                 23 
               
               
                 27.8 ± 0.1 
                 3.210 ± 0.011 
                 43 
               
               
                 28.2 ± 0.1 
                 3.163 ± 0.011 
                 66 
               
               
                 29.0 ± 0.1 
                 3.083 ± 0.010 
                 9 
               
               
                 29.9 ± 0.1 
                 2.992 ± 0.010 
                 22 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malonate has the XRPD pattern as shown in  FIG. 1   b.    
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malonate has the XRPD pattern as shown in  FIG. 73 . 
     Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malonate may also be characterised as having the DSC thermogram as shown in  FIG. 2 . 
     According to another aspect of the present invention, there is provided the camphorsulfonic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione camphorsulfonate or camsylate. 
     In an embodiment, there is provided crystalline Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione camsylate. 
     Form A may be characterised as having an XRPD pattern with a peak at 5.0 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 10.2 and 12.7 °2θ±0.2 °2θ. The XRPD pattern may have yet further peaks at 15.1, 15.6, 16.4, 16.7 and 17.4 °2θ±0.2 °2θ. 
     In an embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 9 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.0 ± 0.1 
                 17.499 ± 0.353  
                 100 
               
               
                 10.2 ± 0.1 
                 8.639 ± 0.085 
                 10 
               
               
                 12.7 ± 0.1 
                 6.954 ± 0.055 
                 25 
               
               
                 15.1 ± 0.1 
                 5.879 ± 0.039 
                 69 
               
               
                 15.6 ± 0.1 
                 5.677 ± 0.036 
                 27 
               
               
                 16.4 ± 0.1 
                 5.418 ± 0.033 
                 31 
               
               
                 16.7 ± 0.1 
                 5.312 ± 0.032 
                 34 
               
               
                 17.4 ± 0.1 
                 5.111 ± 0.029 
                 35 
               
               
                 19.1 ± 0.1 
                 4.642 ± 0.024 
                 42 
               
               
                 20.5 ± 0.1 
                 4.326 ± 0.021 
                 23 
               
               
                 25.7 ± 0.1 
                 3.464 ± 0.013 
                 40 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 10 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 10 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.0 ± 0.1 
                 17.499 ± 0.353  
                 100 
               
               
                  8.5 ± 0.1 
                 10.366 ± 0.123  
                 6 
               
               
                 10.2 ± 0.1 
                 8.639 ± 0.085 
                 10 
               
               
                 12.7 ± 0.1 
                 6.954 ± 0.055 
                 25 
               
               
                 13.8 ± 0.1 
                 6.440 ± 0.047 
                 5 
               
               
                 15.1 ± 0.1 
                 5.879 ± 0.039 
                 69 
               
               
                 15.6 ± 0.1 
                 5.677 ± 0.036 
                 27 
               
               
                 16.4 ± 0.1 
                 5.418 ± 0.033 
                 31 
               
               
                 16.7 ± 0.1 
                 5.312 ± 0.032 
                 34 
               
               
                 17.4 ± 0.1 
                 5.111 ± 0.029 
                 35 
               
               
                 18.1 ± 0.1 
                 4.901 ± 0.027 
                 6 
               
               
                 19.1 ± 0.1 
                 4.642 ± 0.024 
                 42 
               
               
                 19.5 ± 0.1 
                 4.543 ± 0.023 
                 9 
               
               
                 20.5 ± 0.1 
                 4.326 ± 0.021 
                 23 
               
               
                 22.0 ± 0.1 
                 4.046 ± 0.018 
                 7 
               
               
                 22.4 ± 0.1 
                 3.971 ± 0.018 
                 7 
               
               
                 22.7 ± 0.1 
                 3.924 ± 0.017 
                 12 
               
               
                 23.3 ± 0.1 
                 3.824 ± 0.016 
                 11 
               
               
                 24.5 ± 0.1 
                 3.635 ± 0.015 
                 5 
               
               
                 24.9 ± 0.1 
                 3.575 ± 0.014 
                 24 
               
               
                 25.1 ± 0.1 
                 3.545 ± 0.014 
                 23 
               
               
                 25.7 ± 0.1 
                 3.464 ± 0.013 
                 40 
               
               
                 26.5 ± 0.1 
                 3.367 ± 0.013 
                 15 
               
               
                 27.4 ± 0.1 
                 3.252 ± 0.012 
                 8 
               
               
                 28.4 ± 0.1 
                 3.144 ± 0.011 
                 6 
               
               
                 29.2 ± 0.1 
                 3.062 ± 0.010 
                 6 
               
               
                 29.6 ± 0.1 
                 3.013 ± 0.010 
                 5 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione camsylate has the XRPD pattern as shown in  FIG. 1   d.    
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione camsylate has the XRPD pattern as shown in  FIG. 74 . 
     According to another aspect of the present invention, there is provided the fumaric acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione fumarate. 
     In an embodiment, there is provided crystalline Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione fumarate. 
     Form A may be characterised as having an XRPD pattern with peaks at 12.5 and 14.6 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 13.3 and 13.7 °2θ±0.2 °2θ. The XRPD pattern may have yet further peaks at 15.8, 17.5, 22.5 and 23.6 °2θ±0.2 °2θ. 
     In an embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 11 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 11 
               
               
                   
               
               
                   
                   
                 Intensity % 
               
               
                 ° 2θ 
                 d space (Å) 
                 (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 12.5 ± 0.1 
                 7.070 ± 0.057 
                 100 
               
               
                 13.3 ± 0.1 
                 6.642 ± 0.050 
                 15 
               
               
                 13.7 ± 0.1 
                 6.454 ± 0.047 
                 15 
               
               
                 14.6 ± 0.1 
                 6.084 ± 0.042 
                 41 
               
               
                 15.8 ± 0.1 
                 5.602 ± 0.035 
                 44 
               
               
                 17.2 ± 0.1 
                 5.164 ± 0.030 
                 24 
               
               
                 17.5 ± 0.1 
                 5.068 ± 0.029 
                 28 
               
               
                 18.3 ± 0.1 
                 4.838 ± 0.026 
                 17 
               
               
                 20.8 ± 0.1 
                 4.271 ± 0.020 
                 23 
               
               
                 21.3 ± 0.1 
                 4.170 ± 0.019 
                 15 
               
               
                 22.5 ± 0.1 
                 3.955 ± 0.017 
                 77 
               
               
                 23.6 ± 0.1 
                 3.767 ± 0.016 
                 59 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 12 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 12 
               
               
                   
               
               
                 ° 2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 12.5 ± 0.1 
                 7.070 ± 0.057 
                 100 
               
               
                 13.3 ± 0.1 
                 6.642 ± 0.050 
                 15 
               
               
                 13.7 ± 0.1 
                 6.454 ± 0.047 
                 15 
               
               
                 14.6 ± 0.1 
                 6.084 ± 0.042 
                 41 
               
               
                 15.8 ± 0.1 
                 5.602 ± 0.035 
                 44 
               
               
                 17.2 ± 0.1 
                 5.164 ± 0.030 
                 24 
               
               
                 17.5 ± 0.1 
                 5.068 ± 0.029 
                 28 
               
               
                 18.3 ± 0.1 
                 4.838 ± 0.026 
                 17 
               
               
                 19.2 ± 0.1 
                 4.620 ± 0.024 
                 7 
               
               
                 20.3 ± 0.1 
                 4.383 ± 0.022 
                 6 
               
               
                 20.8 ± 0.1 
                 4.271 ± 0.020 
                 23 
               
               
                 21.3 ± 0.1 
                 4.170 ± 0.019 
                 15 
               
               
                 22.5 ± 0.1 
                 3.955 ± 0.017 
                 77 
               
               
                 23.6 ± 0.1 
                 3.767 ± 0.016 
                 59 
               
               
                 24.6 ± 0.1 
                 3.617 ± 0.015 
                 11 
               
               
                 26.3 ± 0.1 
                 3.390 ± 0.013 
                 28 
               
               
                 26.8 ± 0.1 
                 3.327 ± 0.012 
                 23 
               
               
                 27.1 ± 0.1 
                 3.294 ± 0.012 
                 24 
               
               
                 27.6 ± 0.1 
                 3.234 ± 0.012 
                 8 
               
               
                 28.2 ± 0.1 
                 3.160 ± 0.011 
                 16 
               
               
                 28.8 ± 0.1 
                 3.099 ± 0.011 
                 15 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione fumarate has the XRPD pattern as shown in  FIG. 1   e.    
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione fumarate has the XRPD pattern as shown in  FIG. 75 . 
     According to another aspect of the present invention, there is provided the toluenesulfonic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. 
     In an embodiment, there is provided crystalline Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. 
     Form A may be characterised as having an XRPD pattern with peaks at 7.3, 9.2 and 14.6 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 10.8, 13.8 and 14.9 °2θ±0.2 °2θ. 
     The XRPD pattern may have still further peaks at 16.1, 22.0 and 25.0 °2θ±0.2°θ. 
     In an embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 13 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 13 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 7.3 ± 0.1 
                 12.110 ± 0.168  
                 39 
               
               
                 9.2 ± 0.1 
                 9.561 ± 0.104 
                 31 
               
               
                 14.6 ± 0.1  
                 6.059 ± 0.042 
                 81 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form A has an XRPD pattern with peaks at the positions listed in Table 14 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 14 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  7.3 ± 0.1 
                 12.110 ± 0.168  
                 39 
               
               
                  8.1 ± 0.1 
                 10.862 ± 0.135  
                 11 
               
               
                  9.2 ± 0.1 
                 9.561 ± 0.104 
                 31 
               
               
                 10.8 ± 0.1 
                 8.207 ± 0.077 
                 21 
               
               
                 12.5 ± 0.1 
                 7.104 ± 0.057 
                 10 
               
               
                 13.2 ± 0.1 
                 6.687 ± 0.051 
                 11 
               
               
                 13.8 ± 0.1 
                 6.426 ± 0.047 
                 50 
               
               
                 14.6 ± 0.1 
                 6.059 ± 0.042 
                 81 
               
               
                 14.9 ± 0.1 
                 5.938 ± 0.040 
                 87 
               
               
                 16.1 ± 0.1 
                 5.498 ± 0.034 
                 88 
               
               
                 16.7 ± 0.1 
                 5.321 ± 0.032 
                 21 
               
               
                 17.1 ± 0.1 
                 5.192 ± 0.030 
                 15 
               
               
                 18.6 ± 0.1 
                 4.783 ± 0.026 
                 14 
               
               
                 18.9 ± 0.1 
                 4.686 ± 0.025 
                 11 
               
               
                 20.2 ± 0.1 
                 4.390 ± 0.022 
                 23 
               
               
                 21.3 ± 0.1 
                 4.175 ± 0.019 
                 37 
               
               
                 22.0 ± 0.1 
                 4.035 ± 0.018 
                 100 
               
               
                 25.0 ± 0.1 
                 3.558 ± 0.014 
                 94 
               
               
                 25.4 ± 0.1 
                 3.500 ± 0.014 
                 60 
               
               
                 26.0 ± 0.1 
                 3.421 ± 0.013 
                 21 
               
               
                 27.0 ± 0.1 
                 3.305 ± 0.012 
                 25 
               
               
                 27.7 ± 0.1 
                 3.224 ± 0.011 
                 38 
               
               
                 28.6 ± 0.1 
                 3.121 ± 0.011 
                 16 
               
               
                 29.4 ± 0.1 
                 3.037 ± 0.010 
                 36 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 6   a.    
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 76 . 
     In another embodiment, there is provided crystalline Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. 
     Form B may be characterised as having an XRPD pattern with peaks at 4.6, 8.3, 9.0 and 15.0 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 16.0 and 17.7 °2θ±0.2 °2θ. 
     In an embodiment, Form B has an XRPD pattern with peaks at the positions listed in Table 15 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 15 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.086 ± 0.421  
                 100 
               
               
                  8.3 ± 0.1 
                 10.666 ± 0.130  
                 15 
               
               
                  9.0 ± 0.1 
                 9.848 ± 0.111 
                 11 
               
               
                 15.0 ± 0.1 
                 5.891 ± 0.039 
                 15 
               
               
                 16.0 ± 0.1 
                 5.529 ± 0.034 
                 37 
               
               
                 17.7 ± 0.1 
                 5.008 ± 0.028 
                 15 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form B has an XRPD pattern with peaks at the positions listed in Table 16 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 16 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.086 ± 0.421  
                 100 
               
               
                  8.3 ± 0.1 
                 10.666 ± 0.130  
                 15 
               
               
                  9.0 ± 0.1 
                 9.848 ± 0.111 
                 11 
               
               
                 13.2 ± 0.1 
                 6.702 ± 0.051 
                 3 
               
               
                 14.0 ± 0.1 
                 6.344 ± 0.046 
                 3 
               
               
                 15.0 ± 0.1 
                 5.891 ± 0.039 
                 15 
               
               
                 15.5 ± 0.1 
                 5.732 ± 0.037 
                 8 
               
               
                 16.0 ± 0.1 
                 5.529 ± 0.034 
                 37 
               
               
                 16.5 ± 0.1 
                 5.360 ± 0.032 
                 9 
               
               
                 17.1 ± 0.1 
                 5.173 ± 0.030 
                 8 
               
               
                 17.7 ± 0.1 
                 5.008 ± 0.028 
                 15 
               
               
                 18.8 ± 0.1 
                 4.730 ± 0.025 
                 3 
               
               
                 19.9 ± 0.1 
                 4.468 ± 0.022 
                 4 
               
               
                 20.9 ± 0.1 
                 4.252 ± 0.020 
                 6 
               
               
                 21.8 ± 0.1 
                 4.079 ± 0.019 
                 4 
               
               
                 22.5 ± 0.1 
                 3.950 ± 0.017 
                 5 
               
               
                 23.2 ± 0.1 
                 3.834 ± 0.016 
                 5 
               
               
                 24.0 ± 0.1 
                 3.716 ± 0.015 
                 9 
               
               
                 24.9 ± 0.1 
                 3.575 ± 0.014 
                 12 
               
               
                 25.3 ± 0.1 
                 3.524 ± 0.014 
                 13 
               
               
                 25.7 ± 0.1 
                 3.468 ± 0.013 
                 15 
               
               
                 26.6 ± 0.1 
                 3.349 ± 0.012 
                 9 
               
               
                 27.0 ± 0.1 
                 3.305 ± 0.012 
                 7 
               
               
                 28.0 ± 0.1 
                 3.187 ± 0.011 
                 4 
               
               
                 28.8 ± 0.1 
                 3.102 ± 0.011 
                 5 
               
               
                 29.9 ± 0.1 
                 2.992 ± 0.010 
                 4 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 6   b.    
     In an embodiment, Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 77 . 
     Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate may also be characterised as having the DSC thermogram as shown in  FIG. 10 . 
     In another embodiment, there is provided crystalline Form C of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. Form C may be characterised as having an XRPD pattern with peaks at 11.8 and 12.1 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 4.8°2θ±0.2 °2θ. The XRPD pattern may have yet further peaks at 17.9, 19.2, 19.7 and 21.0 °2θ±0.2°θ. 
     In an embodiment, Form C has an XRPD pattern with peaks at the positions listed in Table 17 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 17 
               
               
                   
               
               
                   
                   
                 Intensity % 
               
               
                 °2θ 
                 d space (Å) 
                 (I/Io) 
               
               
                   
               
             
            
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 65 
               
               
                 12.1 ± 0.1 
                 7.297 ± 0.060 
                 23 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form C has an XRPD pattern with peaks at the positions listed in Table 18 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 18 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.8 ± 0.1 
                 18.372 ± 0.390  
                 100 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 65 
               
               
                 12.1 ± 0.1 
                 7.297 ± 0.060 
                 23 
               
               
                 17.9 ± 0.1 
                 4.966 ± 0.028 
                 28 
               
               
                 19.2 ± 0.1 
                 4.620 ± 0.024 
                 25 
               
               
                 19.7 ± 0.1 
                 4.509 ± 0.023 
                 69 
               
               
                 21.0 ± 0.1 
                 4.222 ± 0.020 
                 51 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form C has an XRPD pattern with peaks at the positions listed in Table 19 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 19 
               
               
                   
               
               
                   
                   
                 Intensity 
               
               
                 °2θ 
                 d space (Å) 
                 % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.8 ± 0.1 
                 18.372 ± 0.390  
                 100 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 65 
               
               
                 12.1 ± 0.1 
                 7.297 ± 0.060 
                 23 
               
               
                 13.2 ± 0.1 
                 6.718 ± 0.051 
                 5 
               
               
                 14.0 ± 0.1 
                 6.330 ± 0.045 
                 4 
               
               
                 14.8 ± 0.1 
                 5.998 ± 0.041 
                 6 
               
               
                 15.1 ± 0.1 
                 5.879 ± 0.039 
                 13 
               
               
                 16.1 ± 0.1 
                 5.498 ± 0.034 
                 10 
               
               
                 17.3 ± 0.1 
                 5.129 ± 0.030 
                 7 
               
               
                 17.9 ± 0.1 
                 4.966 ± 0.028 
                 28 
               
               
                 19.2 ± 0.1 
                 4.620 ± 0.024 
                 25 
               
               
                 19.7 ± 0.1 
                 4.509 ± 0.023 
                 69 
               
               
                 20.4 ± 0.1 
                 4.358 ± 0.021 
                 11 
               
               
                 20.8 ± 0.1 
                 4.277 ± 0.020 
                 27 
               
               
                 21.0 ± 0.1 
                 4.222 ± 0.020 
                 51 
               
               
                 21.6 ± 0.1 
                 4.118 ± 0.019 
                 11 
               
               
                 22.4 ± 0.1 
                 3.966 ± 0.018 
                 10 
               
               
                 23.0 ± 0.1 
                 3.859 ± 0.017 
                 17 
               
               
                 24.1 ± 0.1 
                 3.693 ± 0.015 
                 18 
               
               
                 24.9 ± 0.1 
                 3.575 ± 0.014 
                 27 
               
               
                 25.2 ± 0.1 
                 3.541 ± 0.014 
                 24 
               
               
                 25.8 ± 0.1 
                 3.456 ± 0.013 
                 11 
               
               
                 26.3 ± 0.1 
                 3.394 ± 0.013 
                 6 
               
               
                 27.0 ± 0.1 
                 3.308 ± 0.012 
                 9 
               
               
                 27.6 ± 0.1 
                 3.231 ± 0.012 
                 14 
               
               
                 29.5 ± 0.1 
                 3.031 ± 0.010 
                 10 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form C of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 6   c.    
     In an embodiment, Form C of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 78 . 
     Form C of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate may be characterised as having the DSC thermogram as shown in  FIG. 12 . 
     In another embodiment, Form C of the tosylate salt is characterised as being in the form of a solvate of isopropanol. The number of moles of isopropanol per mole of Form C may range from 0.5 to 2.0. Typically, the number of moles ranges from 0.8 to 1.5, more typically from 1 to 1.5. In an embodiment, there is 0.91 mole of isopropanol per 1 mole of Form C. 
     In another embodiment, there is provided crystalline Form E of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. 
     Form E may be characterised as having an XRPD pattern with a peak at 9.7 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 24.6 °2θ±0.2 °2θ. The XRPD pattern may have yet further peaks at 4.9 and 8.1 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 15.8 °2θ±0.2°θ. The XRPD pattern may have yet a further peak at 17.9 °2θ±0.2°θ. 
     In an embodiment, Form E has an XRPD pattern with peaks at the positions listed in Table 20 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 20 
               
               
                   
               
               
                   
                   
                 Intensity 
               
               
                 °2θ 
                 d space (Å) 
                 % (I/Io) 
               
               
                   
               
             
            
               
                  9.7 ± 0.1 
                 9.073 ± 0.094 
                 18 
               
               
                 24.6 ± 0.1 
                 3.613 ± 0.014 
                 54 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form E has an XRPD pattern with peaks at the positions listed in Table 21 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 21 
               
               
                   
               
               
                   
                   
                 Intensity 
               
               
                 °2θ 
                 d space (Å) 
                 % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.9 ± 0.1 
                 17.916 ± 0.371  
                 100 
               
               
                  8.1 ± 0.1 
                 10.935 ± 0.137  
                 22 
               
               
                  9.7 ± 0.1 
                 9.073 ± 0.094 
                 18 
               
               
                 15.8 ± 0.1 
                 5.593 ± 0.035 
                 67 
               
               
                 24.6 ± 0.1 
                 3.613 ± 0.014 
                 54 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form E has an XRPD pattern with peaks at the positions listed in Table 22 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 22 
               
               
                   
               
               
                   
                   
                 Intensity 
               
               
                 °2θ 
                 d space (Å) 
                 % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.4 ± 0.1 
                 25.927 ± 0.784  
                 4 
               
               
                  4.9 ± 0.1 
                 17.916 ± 0.371  
                 100 
               
               
                  5.5 ± 0.1 
                 16.107 ± 0.299  
                 11 
               
               
                  8.1 ± 0.1 
                 10.935 ± 0.137  
                 22 
               
               
                  9.7 ± 0.1 
                 9.073 ± 0.094 
                 18 
               
               
                 13.2 ± 0.1 
                 6.719 ± 0.051 
                 6 
               
               
                 13.8 ± 0.1 
                 6.433 ± 0.047 
                 6 
               
               
                 15.2 ± 0.1 
                 5.834 ± 0.038 
                 12 
               
               
                 15.8 ± 0.1 
                 5.593 ± 0.035 
                 67 
               
               
                 16.2 ± 0.1 
                 5.486 ± 0.034 
                 16 
               
               
                 16.5 ± 0.1 
                 5.361 ± 0.032 
                 18 
               
               
                 17.4 ± 0.1 
                 5.106 ± 0.029 
                 5 
               
               
                 17.9 ± 0.1 
                 4.949 ± 0.028 
                 25 
               
               
                 18.5 ± 0.1 
                 4.802 ± 0.026 
                 22 
               
               
                 19.5 ± 0.1 
                 4.549 ± 0.023 
                 15 
               
               
                 19.7 ± 0.1 
                 4.501 ± 0.023 
                 14 
               
               
                 20.7 ± 0.1 
                 4.285 ± 0.021 
                 21 
               
               
                 21.1 ± 0.1 
                 4.216 ± 0.020 
                 27 
               
               
                 21.5 ± 0.1 
                 4.129 ± 0.019 
                 31 
               
               
                 22.0 ± 0.1 
                 4.045 ± 0.018 
                 17 
               
               
                 22.6 ± 0.1 
                 3.935 ± 0.017 
                 5 
               
               
                 23.4 ± 0.1 
                 3.797 ± 0.016 
                 21 
               
               
                 23.8 ± 0.1 
                 3.732 ± 0.015 
                 11 
               
               
                 24.6 ± 0.1 
                 3.613 ± 0.014 
                 54 
               
               
                 25.2 ± 0.1 
                 3.540 ± 0.014 
                 24 
               
               
                 25.8 ± 0.1 
                 3.447 ± 0.013 
                 17 
               
               
                 26.3 ± 0.1 
                 3.384 ± 0.013 
                 26 
               
               
                 27.8 ± 0.1 
                 3.215 ± 0.011 
                 13 
               
               
                 28.2 ± 0.1 
                 3.164 ± 0.011 
                 14 
               
               
                 29.0 ± 0.1 
                 3.076 ± 0.010 
                 13 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form E of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 6   e.    
     In an embodiment, Form E of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 79 . 
     Form E of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate may also be characterised as having the DSC thermogram as shown in  FIG. 15 . 
     In another embodiment, Form E of the tosylate salt is characterised as being in the form of a solvate of trifluoroethanol. The number of moles of trifluoroethanol per mole of Form E may range from 0.13 to 0.5. Typically, the number of moles ranges from 0.14 to 0.33. In an embodiment, there is 0.143 mole of trifluoroethanol per 1 mole of Form E. 
     In another embodiment, there is provided a crystal modification of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. This crystal modification is hereinafter referred to as crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. 
     Crystal modification X may be characterised as having an XRPD pattern with peaks at 4.8 and 5.4 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 15.6, 16.7 and 25.0 °2θ±0.2 °2θ. 
     In an embodiment, crystal modification X has an XRPD pattern with peaks at the positions listed in Table 23 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 23 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.8 ± 0.1 
                 18.258 ± 0.385  
                 100 
               
               
                  5.4 ± 0.1 
                 16.519 ± 0.314  
                 61 
               
               
                 15.6 ± 0.1 
                 5.666 ± 0.036 
                 95 
               
               
                 16.7 ± 0.1 
                 5.312 ± 0.032 
                 41 
               
               
                 25.0 ± 0.1 
                 3.566 ± 0.014 
                 61 
               
               
                   
               
            
           
         
       
     
     In another embodiment, crystal modification X has an XRPD pattern with peaks at the positions listed in Table 24 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 24 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  2.8 ± 0.1 
                 31.220 ± 1.143  
                 10 
               
               
                  3.6 ± 0.1 
                 24.889 ± 0.721  
                 16 
               
               
                  4.8 ± 0.1 
                 18.258 ± 0.385  
                 100 
               
               
                  5.4 ± 0.1 
                 16.519 ± 0.314  
                 61 
               
               
                  8.5 ± 0.1 
                 10.440 ± 0.125  
                 15 
               
               
                  9.0 ± 0.1 
                 9.881 ± 0.111 
                 15 
               
               
                 10.4 ± 0.1 
                 8.490 ± 0.082 
                 18 
               
               
                 13.2 ± 0.1 
                 6.702 ± 0.051 
                 10 
               
               
                 14.1 ± 0.1 
                 6.264 ± 0.044 
                 14 
               
               
                 15.6 ± 0.1 
                 5.666 ± 0.036 
                 95 
               
               
                 16.2 ± 0.1 
                 5.488 ± 0.034 
                 52 
               
               
                 16.7 ± 0.1 
                 5.312 ± 0.032 
                 41 
               
               
                 18.5 ± 0.1 
                 4.791 ± 0.026 
                 14 
               
               
                 19.5 ± 0.1 
                 4.557 ± 0.023 
                 16 
               
               
                 25.0 ± 0.1 
                 3.566 ± 0.014 
                 61 
               
               
                 25.8 ± 0.1 
                 3.456 ± 0.013 
                 33 
               
               
                   
               
            
           
         
       
     
     In an embodiment, crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate the XRPD pattern as shown in  FIG. 6   f.    
     In an embodiment, crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate the XRPD pattern as shown in  FIG. 80 . 
     Crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate may also be characterised as having the DSC thermogram as shown in  FIG. 17 . 
     In another embodiment, there is provided crystalline Form G of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. 
     Form G may be characterised as having an XRPD pattern with peaks at 3.6, 4.4, 5.3 and 14.2 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 7.1, 9.0 and 13.3 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 15.7 °2θ±0.2°θ. 
     In an embodiment, Form G has an XRPD pattern with peaks at the positions listed in Table 25 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 25 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 3.6 ± 0.1 
                 24.681 ± 0.709 
                 69 
               
               
                 4.4 ± 0.1 
                 19.992 ± 0.463 
                 27 
               
               
                 5.3 ± 0.1 
                 16.706 ± 0.322 
                 88 
               
               
                 14.2 ± 0.1  
                  6.237 ± 0.044 
                 38 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form G has an XRPD pattern with peaks at the positions listed in Table 26 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 26 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.6 ± 0.1 
                 24.681 ± 0.709  
                 69 
               
               
                  4.4 ± 0.1 
                 19.992 ± 0.463  
                 27 
               
               
                  5.3 ± 0.1 
                 16.706 ± 0.322  
                 88 
               
               
                  7.1 ± 0.1 
                 12.468 ± 0.178  
                 15 
               
               
                  9.0 ± 0.1 
                 9.881 ± 0.111 
                 26 
               
               
                 13.3 ± 0.1 
                 6.657 ± 0.050 
                 21 
               
               
                 14.2 ± 0.1 
                 6.237 ± 0.044 
                 38 
               
               
                 15.7 ± 0.1 
                 5.655 ± 0.036 
                 72 
               
               
                 21.0 ± 0.1 
                 4.228 ± 0.020 
                 91 
               
               
                 25.1 ± 0.1 
                 3.545 ± 0.014 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form G has an XRPD pattern with peaks at the positions listed in Table 27 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 27 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.6 ± 0.1 
                 24.681 ± 0.709  
                 69 
               
               
                  4.4 ± 0.1 
                 19.992 ± 0.463  
                 27 
               
               
                  5.3 ± 0.1 
                 16.706 ± 0.322  
                 88 
               
               
                  6.1 ± 0.1 
                 14.561 ± 0.244  
                 10 
               
               
                  7.1 ± 0.1 
                 12.468 ± 0.178  
                 15 
               
               
                  9.0 ± 0.1 
                 9.881 ± 0.111 
                 26 
               
               
                 10.7 ± 0.1 
                 8.276 ± 0.078 
                 15 
               
               
                 11.1 ± 0.1 
                 7.986 ± 0.073 
                 12 
               
               
                 13.3 ± 0.1 
                 6.657 ± 0.050 
                 21 
               
               
                 14.2 ± 0.1 
                 6.237 ± 0.044 
                 38 
               
               
                 15.0 ± 0.1 
                 5.914 ± 0.040 
                 33 
               
               
                 15.7 ± 0.1 
                 5.655 ± 0.036 
                 72 
               
               
                 16.3 ± 0.1 
                 5.438 ± 0.033 
                 59 
               
               
                 17.7 ± 0.1 
                 5.000 ± 0.028 
                 16 
               
               
                 19.2 ± 0.1 
                 4.620 ± 0.024 
                 18 
               
               
                 20.1 ± 0.1 
                 4.416 ± 0.022 
                 32 
               
               
                 21.0 ± 0.1 
                 4.228 ± 0.020 
                 91 
               
               
                 25.1 ± 0.1 
                 3.545 ± 0.014 
                 100 
               
               
                 26.6 ± 0.1 
                 3.345 ± 0.012 
                 22 
               
               
                 27.2 ± 0.1 
                 3.273 ± 0.012 
                 26 
               
               
                 28.1 ± 0.1 
                 3.177 ± 0.011 
                 14 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form G of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 6   g.    
     In an embodiment, Form G of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 81 . 
     In another embodiment, there is provided another crystal modification of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. This crystal modification is hereinafter referred to as crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate. 
     Crystal modification Y may be characterised as having an XRPD pattern with peaks at 4.7 and 11.8 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 17.7, 19.2, 19.9 and 20.8 °2θ±0.2 °2θ. 
     In an embodiment, crystal modification Y has an XRPD pattern with peaks at the positions listed in Table 28 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 28 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.7 ± 0.1 
                 18.722 ± 0.405  
                 100 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 43 
               
               
                 17.7 ± 0.1 
                 5.000 ± 0.028 
                 18 
               
               
                 19.2 ± 0.1 
                 4.635 ± 0.024 
                 22 
               
               
                 19.9 ± 0.1 
                 4.468 ± 0.022 
                 32 
               
               
                 20.8 ± 0.1 
                 4.277 ± 0.020 
                 44 
               
               
                   
               
            
           
         
       
     
     In another embodiment, crystal modification Y has an XRPD pattern with peaks at the positions listed in Table 29 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 29 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.7 ± 0.1 
                 18.722 ± 0.405  
                 100 
               
               
                  9.6 ± 0.1 
                 9.261 ± 0.098 
                 4 
               
               
                 10.7 ± 0.1 
                 8.299 ± 0.078 
                 4 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 43 
               
               
                 13.1 ± 0.1 
                 6.748 ± 0.052 
                 5 
               
               
                 14.3 ± 0.1 
                 6.198 ± 0.043 
                 5 
               
               
                 14.7 ± 0.1 
                 6.022 ± 0.041 
                 7 
               
               
                 15.9 ± 0.1 
                 5.581 ± 0.035 
                 8 
               
               
                 17.7 ± 0.1 
                 5.000 ± 0.028 
                 18 
               
               
                 19.2 ± 0.1 
                 4.635 ± 0.024 
                 22 
               
               
                 19.9 ± 0.1 
                 4.468 ± 0.022 
                 32 
               
               
                 20.8 ± 0.1 
                 4.277 ± 0.020 
                 44 
               
               
                 22.1 ± 0.1 
                 4.019 ± 0.018 
                 7 
               
               
                 22.4 ± 0.1 
                 3.966 ± 0.018 
                 6 
               
               
                 22.9 ± 0.1 
                 3.884 ± 0.017 
                 7 
               
               
                 24.5 ± 0.1 
                 3.631 ± 0.015 
                 16 
               
               
                 25.2 ± 0.1 
                 3.541 ± 0.014 
                 22 
               
               
                 26.1 ± 0.1 
                 3.417 ± 0.013 
                 10 
               
               
                 27.4 ± 0.1 
                 3.252 ± 0.012 
                 10 
               
               
                 27.9 ± 0.1 
                 3.197 ± 0.011 
                 6 
               
               
                 29.7 ± 0.1 
                 3.010 ± 0.010 
                 8 
               
               
                   
               
            
           
         
       
     
     In an embodiment, crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 6   h.    
     In another embodiment, crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate has the XRPD pattern as shown in  FIG. 82 . 
     Crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate may also be characterised as having the DSC thermogram as shown in  FIG. 20 . In another embodiment, crystal modification Y of the tosylate salt is characterised as being in the form of a solvate of trifluoroethanol. The number of moles of trifluoroethanol per mole of crystal modification Y may range from 0.13 to 0.5. Typically, the number of moles ranges from 0.14 to 0.33. In an embodiment, there is 0.143 mole of trifluoroethanol per 1 mole of crystal modification Y. 
     According to another aspect of the present invention, there is provided the acetic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione acetate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione acetate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 11.0 and 12.9 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 15.2, 16.2, 19.6, 21.0, 21.8 and 22.2 °2θ±0.2 °2θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 30 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 30 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 11.0 ± 0.1 
                 8.029 ± 0.073 
                 32 
               
               
                 12.9 ± 0.1 
                 6.842 ± 0.053 
                 100 
               
               
                 15.2 ± 0.1 
                 5.810 ± 0.038 
                 20 
               
               
                 16.2 ± 0.1 
                 5.478 ± 0.034 
                 62 
               
               
                 19.6 ± 0.1 
                 4.522 ± 0.023 
                 46 
               
               
                 21.0 ± 0.1 
                 4.228 ± 0.020 
                 46 
               
               
                 21.8 ± 0.1 
                 4.068 ± 0.018 
                 37 
               
               
                 22.2 ± 0.1 
                 4.013 ± 0.018 
                 54 
               
               
                 24.8 ± 0.1 
                 3.596 ± 0.014 
                 65 
               
               
                 28.9 ± 0.1 
                 3.086 ± 0.010 
                 67 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 31 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 31 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 11.0 ± 0.1 
                 8.029 ± 0.073 
                 32 
               
               
                 12.9 ± 0.1 
                 6.842 ± 0.053 
                 100 
               
               
                 13.3 ± 0.1 
                 6.657 ± 0.050 
                 34 
               
               
                 13.5 ± 0.1 
                 6.540 ± 0.048 
                 25 
               
               
                 15.2 ± 0.1 
                 5.810 ± 0.038 
                 20 
               
               
                 16.2 ± 0.1 
                 5.478 ± 0.034 
                 62 
               
               
                 18.2 ± 0.1 
                 4.877 ± 0.027 
                 8 
               
               
                 19.2 ± 0.1 
                 4.613 ± 0.024 
                 18 
               
               
                 19.6 ± 0.1 
                 4.522 ± 0.023 
                 46 
               
               
                 21.0 ± 0.1 
                 4.228 ± 0.020 
                 46 
               
               
                 21.8 ± 0.1 
                 4.068 ± 0.018 
                 37 
               
               
                 22.2 ± 0.1 
                 4.013 ± 0.018 
                 54 
               
               
                 23.5 ± 0.1 
                 3.791 ± 0.016 
                 19 
               
               
                 23.9 ± 0.1 
                 3.729 ± 0.015 
                 14 
               
               
                 24.2 ± 0.1 
                 3.679 ± 0.015 
                 10 
               
               
                 24.8 ± 0.1 
                 3.596 ± 0.014 
                 65 
               
               
                 25.4 ± 0.1 
                 3.508 ± 0.014 
                 27 
               
               
                 26.0 ± 0.1 
                 3.432 ± 0.013 
                 15 
               
               
                 26.3 ± 0.1 
                 3.386 ± 0.013 
                 20 
               
               
                 27.1 ± 0.1 
                 3.294 ± 0.012 
                 40 
               
               
                 27.6 ± 0.1 
                 3.227 ± 0.011 
                 29 
               
               
                 28.9 ± 0.1 
                 3.086 ± 0.010 
                 67 
               
               
                 29.4 ± 0.1 
                 3.034 ± 0.010 
                 14 
               
               
                 29.8 ± 0.1 
                 2.998 ± 0.010 
                 14 
               
               
                   
               
            
           
         
       
     
     In a further embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione acetate has the XRPD pattern as shown in  FIG. 21   a . In a yet further embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione acetate has the XRPD pattern as shown in  FIG. 21   b.    
     In a further embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione acetate has the XRPD pattern as shown in  FIG. 83 . 
     Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione acetate may also be characterised as having a DSC thermogram as shown in  FIG. 23 . 
     According to another aspect of the present invention, there is provided the adipic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione adipate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione adipate. 
     Form 1 may be characterised as having an XRPD pattern with a peak at 7.8 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 4.5, 12.6, 13.6 and 15.0 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 19.6 and 21.5 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 32 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 32 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 7.8 ± 0.1 
                 11.277 ± 0.145 
                 100 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 33 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 33 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.5 ± 0.1 
                 19.593 ± 0.444  
                 23 
               
               
                  7.8 ± 0.1 
                 11.277 ± 0.145  
                 100 
               
               
                 12.6 ± 0.1 
                 7.020 ± 0.056 
                 81 
               
               
                 13.6 ± 0.1 
                 6.497 ± 0.048 
                 56 
               
               
                 15.0 ± 0.1 
                 5.891 ± 0.039 
                 96 
               
               
                 19.6 ± 0.1 
                 4.536 ± 0.023 
                 50 
               
               
                 21.5 ± 0.1 
                 4.129 ± 0.019 
                 66 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 34 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 34 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.5 ± 0.1 
                 19.593 ± 0.444  
                 23 
               
               
                  7.8 ± 0.1 
                 11.277 ± 0.145  
                 100 
               
               
                 10.8 ± 0.1 
                 8.207 ± 0.077 
                 11 
               
               
                 12.6 ± 0.1 
                 7.020 ± 0.056 
                 81 
               
               
                 13.0 ± 0.1 
                 6.810 ± 0.053 
                 20 
               
               
                 13.6 ± 0.1 
                 6.497 ± 0.048 
                 56 
               
               
                 14.0 ± 0.1 
                 6.330 ± 0.045 
                 29 
               
               
                 14.4 ± 0.1 
                 6.160 ± 0.043 
                 26 
               
               
                 15.0 ± 0.1 
                 5.891 ± 0.039 
                 96 
               
               
                 15.6 ± 0.1 
                 5.666 ± 0.036 
                 25 
               
               
                 16.5 ± 0.1 
                 5.369 ± 0.032 
                 19 
               
               
                 19.6 ± 0.1 
                 4.536 ± 0.023 
                 50 
               
               
                 20.0 ± 0.1 
                 4.435 ± 0.022 
                 34 
               
               
                 20.6 ± 0.1 
                 4.308 ± 0.021 
                 26 
               
               
                 21.5 ± 0.1 
                 4.129 ± 0.019 
                 66 
               
               
                 22.1 ± 0.1 
                 4.019 ± 0.018 
                 28 
               
               
                 22.7 ± 0.1 
                 3.919 ± 0.017 
                 25 
               
               
                 23.9 ± 0.1 
                 3.720 ± 0.015 
                 55 
               
               
                 24.5 ± 0.1 
                 3.631 ± 0.015 
                 77 
               
               
                 25.0 ± 0.1 
                 3.558 ± 0.014 
                 75 
               
               
                 25.8 ± 0.1 
                 3.456 ± 0.013 
                 28 
               
               
                 27.1 ± 0.1 
                 3.290 ± 0.012 
                 37 
               
               
                 27.9 ± 0.1 
                 3.193 ± 0.011 
                 12 
               
               
                 29.4 ± 0.1 
                 3.043 ± 0.010 
                 28 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione adipate has an XRPD pattern as shown in  FIG. 24   a . In another embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione adipate has an XRPD pattern as shown in  FIG. 24   b.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione adipate has an XRPD pattern as shown in  FIG. 84 . 
     Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione adipate may also be characterised by having a DSC thermogram as shown in  FIG. 26 . 
     According to another aspect of the present invention, there is provided the glutaric acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glutarate. 
     In an embodiment, there is provided Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glutarate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 4.4, 8.0, 10.7, 12.4, 13.6 and 14.2 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 15.5 and 16.1 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 19.1 and 19.8 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 35 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 35 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  4.4 ± 0.1 
                 19.857 ± 0.456  
                 26 
               
               
                  8.0 ± 0.1 
                 11.024 ± 0.139  
                 57 
               
               
                 10.7 ± 0.1 
                 8.299 ± 0.078 
                 18 
               
               
                 12.4 ± 0.1 
                 7.121 ± 0.058 
                 97 
               
               
                 13.6 ± 0.1 
                 6.497 ± 0.048 
                 42 
               
               
                 14.2 ± 0.1 
                 6.250 ± 0.044 
                 26 
               
               
                 15.5 ± 0.1 
                 5.732 ± 0.037 
                 63 
               
               
                 16.1 ± 0.1 
                 5.509 ± 0.034 
                 56 
               
               
                 19.1 ± 0.1 
                 4.656 ± 0.024 
                 29 
               
               
                 19.8 ± 0.1 
                 4.495 ± 0.023 
                 42 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 36 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 36 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.4 ± 0.1 
                 19.857 ± 0.456  
                 26 
               
               
                  8.0 ± 0.1 
                 11.024 ± 0.139  
                 57 
               
               
                  8.9 ± 0.1 
                 9.914 ± 0.112 
                 12 
               
               
                 10.7 ± 0.1 
                 8.299 ± 0.078 
                 18 
               
               
                 11.9 ± 0.1 
                 7.443 ± 0.063 
                 10 
               
               
                 12.4 ± 0.1 
                 7.121 ± 0.058 
                 97 
               
               
                 13.6 ± 0.1 
                 6.497 ± 0.048 
                 42 
               
               
                 14.2 ± 0.1 
                 6.250 ± 0.044 
                 26 
               
               
                 15.5 ± 0.1 
                 5.732 ± 0.037 
                 63 
               
               
                 16.1 ± 0.1 
                 5.509 ± 0.034 
                 56 
               
               
                 19.1 ± 0.1 
                 4.656 ± 0.024 
                 29 
               
               
                 19.8 ± 0.1 
                 4.495 ± 0.023 
                 42 
               
               
                 20.5 ± 0.1 
                 4.326 ± 0.021 
                 23 
               
               
                 21.4 ± 0.1 
                 4.147 ± 0.019 
                 21 
               
               
                 22.1 ± 0.1 
                 4.024 ± 0.018 
                 20 
               
               
                 22.5 ± 0.1 
                 3.950 ± 0.017 
                 18 
               
               
                 22.9 ± 0.1 
                 3.884 ± 0.017 
                 26 
               
               
                 23.9 ± 0.1 
                 3.725 ± 0.015 
                 71 
               
               
                 25.0 ± 0.1 
                 3.562 ± 0.014 
                 62 
               
               
                 25.3 ± 0.1 
                 3.524 ± 0.014 
                 57 
               
               
                 25.7 ± 0.1 
                 3.472 ± 0.013 
                 100 
               
               
                 26.3 ± 0.1 
                 3.386 ± 0.013 
                 23 
               
               
                 27.1 ± 0.1 
                 3.294 ± 0.012 
                 36 
               
               
                 27.9 ± 0.1 
                 3.193 ± 0.011 
                 17 
               
               
                 28.4 ± 0.1 
                 3.137 ± 0.011 
                 8 
               
               
                 29.6 ± 0.1 
                 3.019 ± 0.010 
                 14 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glutarate has the XRPD pattern as shown in  FIG. 35   a . In another embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glutarate has the XRPD pattern as shown in  FIG. 35   b.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glutarate has the XRPD pattern as shown in  FIG. 85 . 
     According to another aspect of the present invention, there is provided the succinic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 4.6, 8.1, and 12.7 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 9.0 °2θ±0.2 °2θ. The XRPD pattern may have yet a further peak at 14.0 °2θ±0.2 °2θ. The XRPD pattern may have yet further peaks at 15.7, 20.5 and 24.7 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 37 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 37 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 4.6 ± 0.1 
                 19.045 ± 0.419  
                 36 
               
               
                 8.1 ± 0.1 
                 10.889 ± 0.136  
                 36 
               
               
                 9.0 ± 0.1 
                 9.826 ± 0.110 
                 14 
               
               
                 12.7 ± 0.1  
                 6.981 ± 0.055 
                 46 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 38 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 38 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.045 ± 0.419  
                 36 
               
               
                  8.1 ± 0.1 
                 10.889 ± 0.136  
                 36 
               
               
                  9.0 ± 0.1 
                 9.826 ± 0.110 
                 14 
               
               
                 10.9 ± 0.1 
                 8.102 ± 0.075 
                 16 
               
               
                 12.7 ± 0.1 
                 6.981 ± 0.055 
                 46 
               
               
                 14.0 ± 0.1 
                 6.344 ± 0.046 
                 47 
               
               
                 15.7 ± 0.1 
                 5.652 ± 0.036 
                 63 
               
               
                 20.5 ± 0.1 
                 4.337 ± 0.021 
                 67 
               
               
                 24.7 ± 0.1 
                 3.607 ± 0.014 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 39 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 39 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.045 ± 0.419  
                 36 
               
               
                  8.1 ± 0.1 
                 10.889 ± 0.136  
                 36 
               
               
                  9.0 ± 0.1 
                 9.826 ± 0.110 
                 14 
               
               
                 10.9 ± 0.1 
                 8.102 ± 0.075 
                 16 
               
               
                 12.7 ± 0.1 
                 6.981 ± 0.055 
                 46 
               
               
                 14.0 ± 0.1 
                 6.344 ± 0.046 
                 47 
               
               
                 14.7 ± 0.1 
                 6.018 ± 0.041 
                 14 
               
               
                 15.7 ± 0.1 
                 5.652 ± 0.036 
                 63 
               
               
                 16.8 ± 0.1 
                 5.290 ± 0.032 
                 14 
               
               
                 18.5 ± 0.1 
                 4.801 ± 0.026 
                 13 
               
               
                 19.7 ± 0.1 
                 4.511 ± 0.023 
                 26 
               
               
                 20.5 ± 0.1 
                 4.337 ± 0.021 
                 67 
               
               
                 21.9 ± 0.1 
                 4.062 ± 0.018 
                 23 
               
               
                 22.8 ± 0.1 
                 3.894 ± 0.017 
                 38 
               
               
                 24.7 ± 0.1 
                 3.607 ± 0.014 
                 100 
               
               
                 25.1 ± 0.1 
                 3.545 ± 0.014 
                 84 
               
               
                 26.0 ± 0.1 
                 3.422 ± 0.013 
                 46 
               
               
                 27.1 ± 0.1 
                 3.288 ± 0.012 
                 50 
               
               
                 28.5 ± 0.1 
                 3.134 ± 0.011 
                 30 
               
               
                 29.0 ± 0.1 
                 3.083 ± 0.010 
                 30 
               
               
                 29.8 ± 0.1 
                 2.994 ± 0.010 
                 28 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate is characterised as having an XRPD pattern as shown in  FIG. 59 . 
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate is characterised as having an XRPD pattern as shown in  FIG. 86 . 
     In another embodiment, there is provided crystalline Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate. 
     Form 2 may be characterised as having an XRPD pattern with a peak at 14.6 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 13.0 and 17.1 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 12.2 and 15.9 °2θ±0.2°θ. The XRPD pattern may have still further peaks at 17.7 and 22.6 °2θ±0.2°θ. 
     In an embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 40 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 40 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 13.0 ± 0.1 
                 6.831 ± 0.053 
                 24 
               
               
                 14.6 ± 0.1 
                 6.084 ± 0.042 
                 75 
               
               
                 17.1 ± 0.1 
                 5.192 ± 0.030 
                 21 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 41 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 41 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 12.2 ± 0.1 
                 7.255 ± 0.060 
                 99 
               
               
                 13.0 ± 0.1 
                 6.831 ± 0.053 
                 24 
               
               
                 14.6 ± 0.1 
                 6.084 ± 0.042 
                 75 
               
               
                 15.9 ± 0.1 
                 5.567 ± 0.035 
                 42 
               
               
                 17.1 ± 0.1 
                 5.192 ± 0.030 
                 21 
               
               
                 17.7 ± 0.1 
                 5.017 ± 0.028 
                 26 
               
               
                 22.6 ± 0.1 
                 3.941 ± 0.017 
                 100 
               
               
                 23.8 ± 0.1 
                 3.733 ± 0.015 
                 56 
               
               
                 24.2 ± 0.1 
                 3.672 ± 0.015 
                 67 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 42 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 42 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 12.2 ± 0.1 
                 7.255 ± 0.060 
                 99 
               
               
                 13.0 ± 0.1 
                 6.831 ± 0.053 
                 24 
               
               
                 13.7 ± 0.1 
                 6.454 ± 0.047 
                 9 
               
               
                 14.6 ± 0.1 
                 6.084 ± 0.042 
                 75 
               
               
                 15.9 ± 0.1 
                 5.567 ± 0.035 
                 42 
               
               
                 17.1 ± 0.1 
                 5.192 ± 0.030 
                 21 
               
               
                 17.7 ± 0.1 
                 5.017 ± 0.028 
                 26 
               
               
                 18.1 ± 0.1 
                 4.896 ± 0.027 
                 15 
               
               
                 19.2 ± 0.1 
                 4.632 ± 0.024 
                 12 
               
               
                 20.7 ± 0.1 
                 4.287 ± 0.021 
                 19 
               
               
                 21.4 ± 0.1 
                 4.145 ± 0.019 
                 25 
               
               
                 22.6 ± 0.1 
                 3.941 ± 0.017 
                 100 
               
               
                 23.8 ± 0.1 
                 3.733 ± 0.015 
                 56 
               
               
                 24.2 ± 0.1 
                 3.672 ± 0.015 
                 67 
               
               
                 25.5 ± 0.1 
                 3.496 ± 0.014 
                 26 
               
               
                 26.2 ± 0.1 
                 3.407 ± 0.013 
                 35 
               
               
                 26.7 ± 0.1 
                 3.341 ± 0.012 
                 28 
               
               
                 27.0 ± 0.1 
                 3.298 ± 0.012 
                 28 
               
               
                 28.9 ± 0.1 
                 3.092 ± 0.011 
                 13 
               
               
                 29.3 ± 0.1 
                 3.046 ± 0.010 
                 17 
               
               
                 29.8 ± 0.1 
                 2.994 ± 0.010 
                 30 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate is characterised as having an XRPD pattern as shown in  FIG. 59 . 
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate is characterised as having an XRPD pattern as shown in  FIG. 87 . 
     In an embodiment, there is provided crystalline Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate. 
     Form 3 may be characterised as having an XRPD pattern with a peak at 7.6 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 3.7 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 11.1, 14.0 and 14.4 °2θ±0.2°θ. The XRPD pattern may have yet further peaks at 15.6, 19.2 and 24.0 °2θ±0.2°θ. 
     In an embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 43 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 43 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 7.6 ± 0.1 
                 11.633 ± 0.155 
                 14 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 44 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 44 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 3.7 ± 0.1 
                 24.076 ± 0.674 
                 13 
               
               
                 7.6 ± 0.1 
                 11.633 ± 0.155 
                 14 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 45 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 45 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.7 ± 0.1 
                 24.076 ± 0.674  
                 13 
               
               
                  7.6 ± 0.1 
                 11.633 ± 0.155  
                 14 
               
               
                 11.1 ± 0.1 
                 7.986 ± 0.073 
                 23 
               
               
                 14.0 ± 0.1 
                 6.344 ± 0.046 
                 18 
               
               
                 14.4 ± 0.1 
                 6.160 ± 0.043 
                 19 
               
               
                 15.2 ± 0.1 
                 5.821 ± 0.038 
                 28 
               
               
                 15.6 ± 0.1 
                 5.677 ± 0.036 
                 35 
               
               
                 16.3 ± 0.1 
                 5.448 ± 0.033 
                 20 
               
               
                 16.8 ± 0.1 
                 5.265 ± 0.031 
                 26 
               
               
                 19.2 ± 0.1 
                 4.628 ± 0.024 
                 56 
               
               
                 24.0 ± 0.1 
                 3.711 ± 0.015 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 46 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 46 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.7 ± 0.1 
                 24.076 ± 0.674  
                 13 
               
               
                  7.6 ± 0.1 
                 11.633 ± 0.155  
                 14 
               
               
                 10.7 ± 0.1 
                 8.299 ± 0.078 
                 12 
               
               
                 11.1 ± 0.1 
                 7.986 ± 0.073 
                 23 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 14 
               
               
                 14.0 ± 0.1 
                 6.344 ± 0.046 
                 18 
               
               
                 14.4 ± 0.1 
                 6.160 ± 0.043 
                 19 
               
               
                 15.2 ± 0.1 
                 5.821 ± 0.038 
                 28 
               
               
                 15.6 ± 0.1 
                 5.677 ± 0.036 
                 35 
               
               
                 16.3 ± 0.1 
                 5.448 ± 0.033 
                 20 
               
               
                 16.8 ± 0.1 
                 5.265 ± 0.031 
                 26 
               
               
                 17.8 ± 0.1 
                 4.983 ± 0.028 
                 4 
               
               
                 19.2 ± 0.1 
                 4.628 ± 0.024 
                 56 
               
               
                 20.0 ± 0.1 
                 4.448 ± 0.022 
                 41 
               
               
                 20.2 ± 0.1 
                 4.396 ± 0.022 
                 35 
               
               
                 21.2 ± 0.1 
                 4.187 ± 0.020 
                 39 
               
               
                 21.7 ± 0.1 
                 4.096 ± 0.019 
                 14 
               
               
                 22.1 ± 0.1 
                 4.030 ± 0.018 
                 14 
               
               
                 23.4 ± 0.1 
                 3.810 ± 0.016 
                 39 
               
               
                 24.0 ± 0.1 
                 3.711 ± 0.015 
                 100 
               
               
                 24.6 ± 0.1 
                 3.617 ± 0.015 
                 29 
               
               
                 25.5 ± 0.1 
                 3.488 ± 0.013 
                 19 
               
               
                 25.8 ± 0.1 
                 3.448 ± 0.013 
                 19 
               
               
                 26.8 ± 0.1 
                 3.330 ± 0.012 
                 21 
               
               
                 27.5 ± 0.1 
                 3.248 ± 0.012 
                 18 
               
               
                 28.0 ± 0.1 
                 3.190 ± 0.011 
                 18 
               
               
                 28.6 ± 0.1 
                 3.124 ± 0.011 
                 13 
               
               
                 29.9 ± 0.1 
                 2.989 ± 0.010 
                 10 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate is characterised as having an XRPD pattern as shown in  FIG. 59 . 
     In an embodiment, Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate is characterised as having an XRPD pattern as shown in  FIG. 88 . 
     According to another aspect of the present invention, there is provided the hydrobromide salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide. 
     Form 1 may be characterised as having an XRPD pattern with a peak at 6.9 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 14.8 °2θ±0.2°2θ. The XRPD pattern may have still further peaks at 13.7, 16.5 and 18.0 °2θ±0.2°θ. The XRPD pattern may have yet further peaks at 22.0 and 27.5 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 47 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 47 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 6.9 ± 0.1 
                 12.848 ± 0.189 
                 23 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 48 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 48 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  6.9 ± 0.1 
                 12.848 ± 0.189  
                 23 
               
               
                 14.8 ± 0.1 
                 5.970 ± 0.040 
                 32 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 49 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 49 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.9 ± 0.1 
                 12.848 ± 0.189  
                 23 
               
               
                 13.7 ± 0.1 
                 6.473 ± 0.047 
                 32 
               
               
                 14.8 ± 0.1 
                 5.970 ± 0.040 
                 32 
               
               
                 16.5 ± 0.1 
                 5.379 ± 0.033 
                 37 
               
               
                 18.0 ± 0.1 
                 4.939 ± 0.027 
                 27 
               
               
                 20.2 ± 0.1 
                 4.388 ± 0.022 
                 27 
               
               
                 21.0 ± 0.1 
                 4.230 ± 0.020 
                 30 
               
               
                 22.0 ± 0.1 
                 4.040 ± 0.018 
                 84 
               
               
                 27.5 ± 0.1 
                 3.246 ± 0.012 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 50 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 50 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.9 ± 0.1 
                 12.848 ± 0.189  
                 23 
               
               
                 13.7 ± 0.1 
                 6.473 ± 0.047 
                 32 
               
               
                 14.8 ± 0.1 
                 5.970 ± 0.040 
                 32 
               
               
                 16.5 ± 0.1 
                 5.379 ± 0.033 
                 37 
               
               
                 18.0 ± 0.1 
                 4.939 ± 0.027 
                 27 
               
               
                 20.2 ± 0.1 
                 4.388 ± 0.022 
                 27 
               
               
                 21.0 ± 0.1 
                 4.230 ± 0.020 
                 30 
               
               
                 22.0 ± 0.1 
                 4.040 ± 0.018 
                 84 
               
               
                 24.0 ± 0.1 
                 3.702 ± 0.015 
                 42 
               
               
                 25.0 ± 0.1 
                 3.556 ± 0.014 
                 59 
               
               
                 25.6 ± 0.1 
                 3.485 ± 0.013 
                 55 
               
               
                 27.5 ± 0.1 
                 3.246 ± 0.012 
                 100 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide is characterised as having an XRPD pattern as shown in  FIG. 40   a . In another embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide is characterised as having an XRPD pattern as shown in  FIG. 40   c.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide is characterised as having an XRPD pattern as shown in  FIG. 89 . 
     Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide may also be characterised by having a DSC thermogram as shown in  FIG. 44 . 
     In an embodiment, there is provided crystalline Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide. 
     Form 2 may be characterised as having an XRPD pattern with peaks at 9.7, 11.8 and 12.3 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 14.5 or 16.0 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 18.7, 23.3 and 26.8 °2θ±0.2°θ. 
     In an embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 51 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 51 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  9.7 ± 0.1 
                 9.137 ± 0.095 
                 23 
               
               
                 11.8 ± 0.1 
                 7.525 ± 0.064 
                 26 
               
               
                 12.3 ± 0.1 
                 7.208 ± 0.059 
                 25 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 52 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 52 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  9.7 ± 0.1 
                 9.137 ± 0.095 
                 23 
               
               
                 11.8 ± 0.1 
                 7.525 ± 0.064 
                 26 
               
               
                 12.3 ± 0.1 
                 7.208 ± 0.059 
                 25 
               
               
                 14.5 ± 0.1 
                 6.117 ± 0.042 
                 28 
               
               
                 16.0 ± 0.1 
                 5.553 ± 0.035 
                 53 
               
               
                 18.7 ± 0.1 
                 4.750 ± 0.025 
                 33 
               
               
                 22.0 ± 0.1 
                 4.048 ± 0.018 
                 51 
               
               
                 23.3 ± 0.1 
                 3.821 ± 0.016 
                 62 
               
               
                 26.8 ± 0.1 
                 3.327 ± 0.012 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 53 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 53 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.8 ± 0.1 
                 18.565 ± 0.398  
                 12 
               
               
                  8.3 ± 0.1 
                 10.627 ± 0.129  
                 14 
               
               
                  9.7 ± 0.1 
                 9.137 ± 0.095 
                 23 
               
               
                 11.8 ± 0.1 
                 7.525 ± 0.064 
                 26 
               
               
                 12.3 ± 0.1 
                 7.208 ± 0.059 
                 25 
               
               
                 13.6 ± 0.1 
                 6.511 ± 0.048 
                 19 
               
               
                 14.5 ± 0.1 
                 6.117 ± 0.042 
                 28 
               
               
                 16.0 ± 0.1 
                 5.553 ± 0.035 
                 53 
               
               
                 18.7 ± 0.1 
                 4.750 ± 0.025 
                 33 
               
               
                 21.6 ± 0.1 
                 4.114 ± 0.019 
                 46 
               
               
                 22.0 ± 0.1 
                 4.048 ± 0.018 
                 51 
               
               
                 23.3 ± 0.1 
                 3.821 ± 0.016 
                 62 
               
               
                 24.0 ± 0.1 
                 3.708 ± 0.015 
                 48 
               
               
                 24.9 ± 0.1 
                 3.579 ± 0.014 
                 51 
               
               
                 26.8 ± 0.1 
                 3.327 ± 0.012 
                 100 
               
               
                 28.5 ± 0.1 
                 3.134 ± 0.011 
                 42 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide is characterised as having an XRPD pattern as shown in  FIG. 40   d.    
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide is characterised as having an XRPD pattern as shown in  FIG. 90 . 
     In an embodiment, there is provided crystalline Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide. 
     Form 3 may be characterised as having an XRPD pattern with peaks at 6.0, 8.9 and 13.2 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 15.1, 15.6 and 16.9 °2θ±0.2°2θ. The XRPD pattern may have still further peaks at 12.1 and 14.5 °2θ±0.2°θ. The XRPD pattern may have still further peaks at 17.9 and 26.2 °2θ±0.2°θ. 
     In an embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 54 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 54 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  6.0 ± 0.1 
                 14.706 ± 0.249  
                 63 
               
               
                  8.9 ± 0.1 
                 9.914 ± 0.112 
                 64 
               
               
                 13.2 ± 0.1 
                 6.702 ± 0.051 
                 23 
               
               
                 15.1 ± 0.1 
                 5.867 ± 0.039 
                 21 
               
               
                 15.6 ± 0.1 
                 5.699 ± 0.037 
                 29 
               
               
                 16.9 ± 0.1 
                 5.256 ± 0.031 
                 37 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 55 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 55 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.0 ± 0.1 
                 14.706 ± 0.249  
                 63 
               
               
                  8.9 ± 0.1 
                 9.914 ± 0.112 
                 64 
               
               
                 12.1 ± 0.1 
                 7.333 ± 0.061 
                 21 
               
               
                 13.2 ± 0.1 
                 6.702 ± 0.051 
                 23 
               
               
                 14.5 ± 0.1 
                 6.109 ± 0.042 
                 26 
               
               
                 15.1 ± 0.1 
                 5.867 ± 0.039 
                 21 
               
               
                 15.6 ± 0.1 
                 5.699 ± 0.037 
                 29 
               
               
                 16.9 ± 0.1 
                 5.256 ± 0.031 
                 37 
               
               
                 17.9 ± 0.1 
                 4.966 ± 0.028 
                 86 
               
               
                 19.3 ± 0.1 
                 4.606 ± 0.024 
                 78 
               
               
                 21.6 ± 0.1 
                 4.118 ± 0.019 
                 64 
               
               
                 25.1 ± 0.1 
                 3.549 ± 0.014 
                 78 
               
               
                 26.2 ± 0.1 
                 3.401 ± 0.013 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 56 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 56 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.0 ± 0.1 
                 14.706 ± 0.249  
                 63 
               
               
                  8.9 ± 0.1 
                 9.914 ± 0.112 
                 64 
               
               
                 12.1 ± 0.1 
                 7.333 ± 0.061 
                 21 
               
               
                 13.2 ± 0.1 
                 6.702 ± 0.051 
                 23 
               
               
                 14.5 ± 0.1 
                 6.109 ± 0.042 
                 26 
               
               
                 15.1 ± 0.1 
                 5.867 ± 0.039 
                 21 
               
               
                 15.6 ± 0.1 
                 5.699 ± 0.037 
                 29 
               
               
                 16.9 ± 0.1 
                 5.256 ± 0.031 
                 37 
               
               
                 17.9 ± 0.1 
                 4.966 ± 0.028 
                 86 
               
               
                 19.3 ± 0.1 
                 4.606 ± 0.024 
                 78 
               
               
                 20.1 ± 0.1 
                 4.422 ± 0.022 
                 23 
               
               
                 20.4 ± 0.1 
                 4.351 ± 0.021 
                 30 
               
               
                 21.6 ± 0.1 
                 4.118 ± 0.019 
                 64 
               
               
                 22.1 ± 0.1 
                 4.024 ± 0.018 
                 33 
               
               
                 23.1 ± 0.1 
                 3.849 ± 0.016 
                 31 
               
               
                 24.4 ± 0.1 
                 3.648 ± 0.015 
                 14 
               
               
                 25.1 ± 0.1 
                 3.549 ± 0.014 
                 78 
               
               
                 25.8 ± 0.1 
                 3.452 ± 0.013 
                 45 
               
               
                 26.2 ± 0.1 
                 3.401 ± 0.013 
                 100 
               
               
                 27.0 ± 0.1 
                 3.308 ± 0.012 
                 49 
               
               
                 27.7 ± 0.1 
                 3.221 ± 0.011 
                 18 
               
               
                 28.7 ± 0.1 
                 3.115 ± 0.011 
                 16 
               
               
                 29.2 ± 0.1 
                 3.062 ± 0.010 
                 17 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide is characterised as having an XRPD pattern as shown in  FIG. 40   b.    
     In an embodiment, Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide is characterised as having an XRPD pattern as shown in  FIG. 91 . 
     According to another aspect of the present invention, there is provided the maleic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 11.3, 14.1 and 14.4 °2θ±0.2°2θ. The XRPD pattern may have a further peak at 9.1 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 15.6 and 16.4 °2θ±0.2°θ. The XRPD pattern may have yet further peaks at 19.7 and 25.2 °θ0±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 57 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 57 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  9.1 ± 0.1 
                 9.697 ± 0.107 
                 14 
               
               
                 11.3 ± 0.1 
                 7.817 ± 0.069 
                 34 
               
               
                 14.1 ± 0.1 
                 6.290 ± 0.045 
                 30 
               
               
                 14.4 ± 0.1 
                 6.134 ± 0.043 
                 31 
               
               
                 15.6 ± 0.1 
                 5.666 ± 0.036 
                 24 
               
               
                 16.4 ± 0.1 
                 5.418 ± 0.033 
                 56 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 58 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 58 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  9.1 ± 0.1 
                 9.697 ± 0.107 
                 14 
               
               
                 11.3 ± 0.1 
                 7.817 ± 0.069 
                 34 
               
               
                 12.5 ± 0.1 
                 7.070 ± 0.057 
                 15 
               
               
                 14.1 ± 0.1 
                 6.290 ± 0.045 
                 30 
               
               
                 14.4 ± 0.1 
                 6.134 ± 0.043 
                 31 
               
               
                 15.6 ± 0.1 
                 5.666 ± 0.036 
                 24 
               
               
                 16.4 ± 0.1 
                 5.418 ± 0.033 
                 56 
               
               
                 19.7 ± 0.1 
                 4.502 ± 0.023 
                 44 
               
               
                 22.8 ± 0.1 
                 3.900 ± 0.017 
                 36 
               
               
                 24.0 ± 0.1 
                 3.702 ± 0.015 
                 70 
               
               
                 25.2 ± 0.1 
                 3.534 ± 0.014 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 59 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 59 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  9.1 ± 0.1 
                 9.697 ± 0.107 
                 14 
               
               
                 10.6 ± 0.1 
                 8.346 ± 0.079 
                 9 
               
               
                 11.3 ± 0.1 
                 7.817 ± 0.069 
                 34 
               
               
                 12.5 ± 0.1 
                 7.070 ± 0.057 
                 15 
               
               
                 13.4 ± 0.1 
                 6.608 ± 0.049 
                 12 
               
               
                 14.1 ± 0.1 
                 6.290 ± 0.045 
                 30 
               
               
                 14.4 ± 0.1 
                 6.134 ± 0.043 
                 31 
               
               
                 15.6 ± 0.1 
                 5.666 ± 0.036 
                 24 
               
               
                 16.4 ± 0.1 
                 5.418 ± 0.033 
                 56 
               
               
                 17.2 ± 0.1 
                 5.156 ± 0.030 
                 15 
               
               
                 17.7 ± 0.1 
                 5.005 ± 0.028 
                 14 
               
               
                 18.6 ± 0.1 
                 4.760 ± 0.025 
                 11 
               
               
                 19.7 ± 0.1 
                 4.502 ± 0.023 
                 44 
               
               
                 20.6 ± 0.1 
                 4.303 ± 0.021 
                 19 
               
               
                 21.0 ± 0.1 
                 4.222 ± 0.020 
                 16 
               
               
                 21.7 ± 0.1 
                 4.092 ± 0.019 
                 21 
               
               
                 22.8 ± 0.1 
                 3.900 ± 0.017 
                 36 
               
               
                 24.0 ± 0.1 
                 3.702 ± 0.015 
                 70 
               
               
                 25.2 ± 0.1 
                 3.534 ± 0.014 
                 100 
               
               
                 26.2 ± 0.1 
                 3.407 ± 0.013 
                 35 
               
               
                 27.2 ± 0.1 
                 3.279 ± 0.012 
                 44 
               
               
                 29.1 ± 0.1 
                 3.067 ± 0.010 
                 20 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate is characterised as having an XRPD pattern as shown in  FIG. 49   b.    
     In an, embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate is characterised as having an XRPD pattern as shown in  FIG. 92 . 
     In an embodiment, there is provided crystalline Form 1+peaks of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate. Hereinafter, this crystalline form shall be referred to as Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate. 
     Form 2 may be characterised as having an XRPD pattern with peaks at 4.0, 8.1, 8.8 and 11.0 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 16.2 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 12.3 and 14.5 °2θ±0.2°θ. The XRPD pattern may have a yet further peak at 15.8 °2θ±0.2°θ. 
     In an embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 60 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 60 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 4.0 ± 0.1 
                 22.090 ± 0.566 
                 100 
               
               
                 8.1 ± 0.1 
                 10.902 ± 0.136 
                 44 
               
               
                 8.8 ± 0.1 
                 10.015 ± 0.114 
                 49 
               
               
                 11.0 ± 0.1  
                  8.073 ± 0.074 
                 49 
               
               
                 16.2 ± 0.1  
                  5.478 ± 0.034 
                 80 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 61 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 61 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.0 ± 0.1 
                 22.090 ± 0.566  
                 100 
               
               
                  8.1 ± 0.1 
                 10.902 ± 0.136  
                 44 
               
               
                  8.8 ± 0.1 
                 10.015 ± 0.114  
                 49 
               
               
                 11.0 ± 0.1 
                 8.073 ± 0.074 
                 49 
               
               
                 12.3 ± 0.1 
                 7.173 ± 0.058 
                 65 
               
               
                 14.5 ± 0.1 
                 6.121 ± 0.042 
                 50 
               
               
                 15.8 ± 0.1 
                 5.623 ± 0.036 
                 67 
               
               
                 16.2 ± 0.1 
                 5.478 ± 0.034 
                 80 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 62 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 62 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.0 ± 0.1 
                 22.090 ± 0.566  
                 100 
               
               
                  8.1 ± 0.1 
                 10.902 ± 0.136  
                 44 
               
               
                  8.8 ± 0.1 
                 10.015 ± 0.114  
                 49 
               
               
                 11.0 ± 0.1 
                 8.073 ± 0.074 
                 49 
               
               
                 11.5 ± 0.1 
                 7.695 ± 0.067 
                 21 
               
               
                 12.3 ± 0.1 
                 7.173 ± 0.058 
                 65 
               
               
                 13.6 ± 0.1 
                 6.525 ± 0.048 
                 22 
               
               
                 14.5 ± 0.1 
                 6.121 ± 0.042 
                 50 
               
               
                 15.8 ± 0.1 
                 5.623 ± 0.036 
                 67 
               
               
                 16.2 ± 0.1 
                 5.478 ± 0.034 
                 80 
               
               
                 16.8 ± 0.1 
                 5.284 ± 0.031 
                 16 
               
               
                 17.7 ± 0.1 
                 5.017 ± 0.028 
                 9 
               
               
                 18.7 ± 0.1 
                 4.745 ± 0.025 
                 8 
               
               
                 19.9 ± 0.1 
                 4.462 ± 0.022 
                 34 
               
               
                 20.9 ± 0.1 
                 4.246 ± 0.020 
                 27 
               
               
                 21.2 ± 0.1 
                 4.193 ± 0.020 
                 40 
               
               
                 22.0 ± 0.1 
                 4.046 ± 0.018 
                 39 
               
               
                 22.8 ± 0.1 
                 3.899 ± 0.017 
                 31 
               
               
                 23.8 ± 0.1 
                 3.734 ± 0.016 
                 42 
               
               
                 24.9 ± 0.1 
                 3.575 ± 0.014 
                 14 
               
               
                 26.3 ± 0.1 
                 3.390 ± 0.013 
                 50 
               
               
                 26.7 ± 0.1 
                 3.338 ± 0.012 
                 95 
               
               
                 27.4 ± 0.1 
                 3.259 ± 0.012 
                 48 
               
               
                 29.6 ± 0.1 
                 3.013 ± 0.010 
                 14 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate is characterised as having an XRPD pattern as shown in  FIG. 49   a.    
     In another embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate is characterised as having an XRPD pattern as shown in  FIG. 93 . 
     According to another aspect of the present invention, there is provided the phosphoric acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 4.6, 8.5, 9.3 and 11.0 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 16.4 °2θ±0.2°2θ. The XRPD pattern may have still further peaks at 21.0, 23.0 and 27.2 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 63 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 63 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.210 ± 0.427  
                 14 
               
               
                  8.5 ± 0.1 
                 10.378 ± 0.123  
                 27 
               
               
                  9.3 ± 0.1 
                 9.530 ± 0.104 
                 30 
               
               
                 11.0 ± 0.1 
                 8.073 ± 0.074 
                 46 
               
               
                 16.4 ± 0.1 
                 5.392 ± 0.033 
                 55 
               
               
                 21.0 ± 0.1 
                 4.238 ± 0.020 
                 40 
               
               
                 23.0 ± 0.1 
                 3.874 ± 0.017 
                 44 
               
               
                 27.2 ± 0.1 
                 3.283 ± 0.012 
                 100 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 64 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 64 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.210 ± 0.427  
                 14 
               
               
                  8.5 ± 0.1 
                 10.378 ± 0.123  
                 27 
               
               
                  9.3 ± 0.1 
                 9.530 ± 0.104 
                 30 
               
               
                 11.0 ± 0.1 
                 8.073 ± 0.074 
                 46 
               
               
                 11.6 ± 0.1 
                 7.629 ± 0.066 
                 12 
               
               
                 12.3 ± 0.1 
                 7.185 ± 0.059 
                 18 
               
               
                 12.8 ± 0.1 
                 6.938 ± 0.055 
                 16 
               
               
                 13.8 ± 0.1 
                 6.417 ± 0.047 
                 15 
               
               
                 14.3 ± 0.1 
                 6.185 ± 0.043 
                 19 
               
               
                 15.3 ± 0.1 
                 5.799 ± 0.038 
                 19 
               
               
                 16.4 ± 0.1 
                 5.392 ± 0.033 
                 55 
               
               
                 18.1 ± 0.1 
                 4.896 ± 0.027 
                 19 
               
               
                 19.4 ± 0.1 
                 4.566 ± 0.023 
                 14 
               
               
                 20.0 ± 0.1 
                 4.431 ± 0.022 
                 20 
               
               
                 21.0 ± 0.1 
                 4.238 ± 0.020 
                 40 
               
               
                 21.7 ± 0.1 
                 4.099 ± 0.019 
                 22 
               
               
                 23.0 ± 0.1 
                 3.874 ± 0.017 
                 44 
               
               
                 24.2 ± 0.1 
                 3.678 ± 0.015 
                 22 
               
               
                 24.8 ± 0.1 
                 3.584 ± 0.014 
                 32 
               
               
                 25.7 ± 0.1 
                 3.469 ± 0.013 
                 25 
               
               
                 27.2 ± 0.1 
                 3.283 ± 0.012 
                 100 
               
               
                 28.7 ± 0.1 
                 3.113 ± 0.011 
                 40 
               
               
                 29.7 ± 0.1 
                 3.006 ± 0.010 
                 16 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 51   a.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 94 . 
     In an embodiment, there is provided crystalline Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     Form 2 may be characterised as having an XRPD pattern with peaks at 4.5, 8.3, 9.0, 10.4, 11.1 and 12.7 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 16.1 and 17.5 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 20.9 °2θ±0.2°θ. 
     In an embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 65 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 65 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.5 ± 0.1 
                 19.724 ± 0.450  
                 27 
               
               
                  8.3 ± 0.1 
                 10.679 ± 0.130  
                 100 
               
               
                  9.0 ± 0.1 
                 9.826 ± 0.110 
                 25 
               
               
                 10.4 ± 0.1 
                 8.539 ± 0.083 
                 18 
               
               
                 11.1 ± 0.1 
                 7.986 ± 0.073 
                 41 
               
               
                 12.7 ± 0.1 
                 6.959 ± 0.055 
                 28 
               
               
                 16.1 ± 0.1 
                 5.512 ± 0.034 
                 53 
               
               
                 17.5 ± 0.1 
                 5.062 ± 0.029 
                 28 
               
               
                 20.9 ± 0.1 
                 4.254 ± 0.020 
                 49 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 66 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 66 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.5 ± 0.1 
                 19.724 ± 0.450  
                 27 
               
               
                  8.3 ± 0.1 
                 10.679 ± 0.130  
                 100 
               
               
                  9.0 ± 0.1 
                 9.826 ± 0.110 
                 25 
               
               
                 10.4 ± 0.1 
                 8.539 ± 0.083 
                 18 
               
               
                 11.1 ± 0.1 
                 7.986 ± 0.073 
                 41 
               
               
                 12.7 ± 0.1 
                 6.959 ± 0.055 
                 28 
               
               
                 13.8 ± 0.1 
                 6.436 ± 0.047 
                 22 
               
               
                 16.1 ± 0.1 
                 5.512 ± 0.034 
                 53 
               
               
                 17.5 ± 0.1 
                 5.062 ± 0.029 
                 28 
               
               
                 18.6 ± 0.1 
                 4.771 ± 0.026 
                 22 
               
               
                 20.4 ± 0.1 
                 4.353 ± 0.021 
                 35 
               
               
                 20.9 ± 0.1 
                 4.254 ± 0.020 
                 49 
               
               
                 21.5 ± 0.1 
                 4.129 ± 0.019 
                 30 
               
               
                 22.2 ± 0.1 
                 3.997 ± 0.018 
                 40 
               
               
                 22.8 ± 0.1 
                 3.894 ± 0.017 
                 35 
               
               
                 24.1 ± 0.1 
                 3.696 ± 0.015 
                 51 
               
               
                 26.2 ± 0.1 
                 3.407 ± 0.013 
                 65 
               
               
                 27.0 ± 0.1 
                 3.298 ± 0.012 
                 65 
               
               
                 27.9 ± 0.1 
                 3.196 ± 0.011 
                 43 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 51   d.    
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 95 . 
     In an embodiment, there is provided crystalline Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     Form 3 may be characterised as having an XRPD pattern with peaks at 8.4, 9.3, 10.7 and 12.6 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 16.2 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 26.5 °2θ±0.2°θ. 
     In an embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 67 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 67 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  8.4 ± 0.1 
                 10.526 ± 0.127  
                 56 
               
               
                  9.3 ± 0.1 
                 9.530 ± 0.104 
                 51 
               
               
                 10.7 ± 0.1 
                 8.253 ± 0.077 
                 28 
               
               
                 12.6 ± 0.1 
                 7.003 ± 0.056 
                 42 
               
               
                 16.2 ± 0.1 
                 5.458 ± 0.034 
                 58 
               
               
                 26.5 ± 0.1 
                 3.366 ± 0.013 
                 100 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 68 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 68 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  8.4 ± 0.1 
                 10.526 ± 0.127  
                 56 
               
               
                  9.3 ± 0.1 
                 9.530 ± 0.104 
                 51 
               
               
                 10.7 ± 0.1 
                 8.253 ± 0.077 
                 28 
               
               
                 11.5 ± 0.1 
                 7.708 ± 0.068 
                 18 
               
               
                 12.6 ± 0.1 
                 7.003 ± 0.056 
                 42 
               
               
                 13.7 ± 0.1 
                 6.454 ± 0.047 
                 21 
               
               
                 15.2 ± 0.1 
                 5.829 ± 0.038 
                 25 
               
               
                 16.2 ± 0.1 
                 5.458 ± 0.034 
                 58 
               
               
                 18.1 ± 0.1 
                 4.907 ± 0.027 
                 33 
               
               
                 20.1 ± 0.1 
                 4.422 ± 0.022 
                 40 
               
               
                 20.8 ± 0.1 
                 4.271 ± 0.020 
                 31 
               
               
                 21.4 ± 0.1 
                 4.160 ± 0.019 
                 45 
               
               
                 21.7 ± 0.1 
                 4.099 ± 0.019 
                 39 
               
               
                 22.3 ± 0.1 
                 3.983 ± 0.018 
                 39 
               
               
                 22.9 ± 0.1 
                 3.880 ± 0.017 
                 38 
               
               
                 24.7 ± 0.1 
                 3.602 ± 0.014 
                 47 
               
               
                 25.4 ± 0.1 
                 3.501 ± 0.014 
                 43 
               
               
                 26.5 ± 0.1 
                 3.366 ± 0.013 
                 100 
               
               
                 27.7 ± 0.1 
                 3.218 ± 0.011 
                 40 
               
               
                 28.4 ± 0.1 
                 3.138 ± 0.011 
                 35 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 51   e.    
     In an embodiment, Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 96 . 
     In an embodiment, there is provided crystalline Form 4 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     Form 4 may be characterised as having an XRPD pattern with peaks at 4.3, 10.8 and 13.1 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 17.2 and 20.5 °2θ±0.2°2θ. 
     In an embodiment, Form 4 has an XRPD pattern with peaks at the positions listed in Table 69 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 69 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.3 ± 0.1 
                 20.646 ± 0.494  
                 89 
               
               
                 10.8 ± 0.1 
                 8.192 ± 0.076 
                 53 
               
               
                 13.1 ± 0.1 
                 6.769 ± 0.052 
                 55 
               
               
                 17.2 ± 0.1 
                 5.144 ± 0.030 
                 100 
               
               
                 20.5 ± 0.1 
                 4.328 ± 0.021 
                 89 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 4 has an XRPD pattern with peaks at the positions listed in Table 70 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 70 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.3 ± 0.1 
                 20.646 ± 0.494  
                 89 
               
               
                 10.8 ± 0.1 
                 8.192 ± 0.076 
                 53 
               
               
                 13.1 ± 0.1 
                 6.769 ± 0.052 
                 55 
               
               
                 15.9 ± 0.1 
                 5.567 ± 0.035 
                 40 
               
               
                 17.2 ± 0.1 
                 5.144 ± 0.030 
                 100 
               
               
                 17.7 ± 0.1 
                 5.005 ± 0.028 
                 52 
               
               
                 18.8 ± 0.1 
                 4.720 ± 0.025 
                 57 
               
               
                 20.1 ± 0.1 
                 4.413 ± 0.022 
                 59 
               
               
                 20.5 ± 0.1 
                 4.328 ± 0.021 
                 89 
               
               
                 21.7 ± 0.1 
                 4.092 ± 0.019 
                 78 
               
               
                 22.2 ± 0.1 
                 4.012 ± 0.018 
                 83 
               
               
                 22.4 ± 0.1 
                 3.969 ± 0.018 
                 83 
               
               
                 23.6 ± 0.1 
                 3.770 ± 0.016 
                 67 
               
               
                 24.4 ± 0.1 
                 3.642 ± 0.015 
                 64 
               
               
                 25.4 ± 0.1 
                 3.507 ± 0.014 
                 71 
               
               
                 27.6 ± 0.1 
                 3.232 ± 0.012 
                 60 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 4 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 51   f.    
     In an embodiment, Form 4 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 97 . 
     In an embodiment, there is provided a crystal modification of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. This crystal modification is hereinafter referred to as crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     Crystal modification X may be characterised as having an XRPD pattern with peaks at 4.6, 9.2, 12.5, 15.2 and 15.9 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 16.6, 18.1 and 21.3 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 26.1 °2θ±0.2°θ. 
     In an embodiment, crystal modification X has an XRPD pattern with peaks at the positions listed in Table 71 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 71 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.336 ± 0.432  
                 71 
               
               
                  9.2 ± 0.1 
                 9.623 ± 0.106 
                 53 
               
               
                 12.5 ± 0.1 
                 7.104 ± 0.057 
                 51 
               
               
                 15.2 ± 0.1 
                 5.833 ± 0.038 
                 47 
               
               
                 15.9 ± 0.1 
                 5.581 ± 0.035 
                 55 
               
               
                 16.6 ± 0.1 
                 5.350 ± 0.032 
                 77 
               
               
                 18.1 ± 0.1 
                 4.901 ± 0.027 
                 89 
               
               
                 21.3 ± 0.1 
                 4.175 ± 0.019 
                 56 
               
               
                 26.1 ± 0.1 
                 3.417 ± 0.013 
                 100 
               
               
                   
               
            
           
         
       
     
     In another embodiment, crystal modification X has an XRPD pattern with peaks at the positions listed in Table 72 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 72 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.336 ± 0.432  
                 71 
               
               
                  9.2 ± 0.1 
                 9.623 ± 0.106 
                 53 
               
               
                 12.5 ± 0.1 
                 7.104 ± 0.057 
                 51 
               
               
                 15.2 ± 0.1 
                 5.833 ± 0.038 
                 47 
               
               
                 15.9 ± 0.1 
                 5.581 ± 0.035 
                 55 
               
               
                 16.6 ± 0.1 
                 5.350 ± 0.032 
                 77 
               
               
                 18.1 ± 0.1 
                 4.901 ± 0.027 
                 89 
               
               
                 20.8 ± 0.1 
                 4.265 ± 0.020 
                 39 
               
               
                 21.3 ± 0.1 
                 4.175 ± 0.019 
                 56 
               
               
                 22.8 ± 0.1 
                 3.894 ± 0.017 
                 47 
               
               
                 23.5 ± 0.1 
                 3.791 ± 0.016 
                 46 
               
               
                 23.8 ± 0.1 
                 3.734 ± 0.016 
                 47 
               
               
                 24.6 ± 0.1 
                 3.622 ± 0.015 
                 51 
               
               
                 25.2 ± 0.1 
                 3.529 ± 0.014 
                 59 
               
               
                 26.1 ± 0.1 
                 3.417 ± 0.013 
                 100 
               
               
                 26.3 ± 0.1 
                 3.394 ± 0.013 
                 79 
               
               
                   
               
            
           
         
       
     
     In an embodiment, crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 51   g.    
     In another embodiment, crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 98 . 
     In an embodiment, there is provided crystalline Form 6 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     Form 6 may be characterised as having an XRPD pattern with a peak at 6.6 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 3.3 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 11.8, 12.1 and 13.2 °2θ±0.2°2θ. The XRPD pattern may have still further peaks at 17.8, 20.1 and 22.2 °2θ±0.2°θ. 
     In an embodiment, Form 6 has an XRPD pattern with peaks at the positions listed in Table 73 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 73 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 6.6 ± 0.1 
                 13.433 ± 0.207 
                 46 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 6 has an XRPD pattern with peaks at the positions listed in Table 74 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 74 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 3.3 ± 0.1 
                 26.454 ± 0.816 
                 100 
               
               
                 6.6 ± 0.1 
                 13.433 ± 0.207 
                 46 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 6 has an XRPD pattern with peaks at the positions listed in Table 75 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 75 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.3 ± 0.1 
                 26.454 ± 0.816  
                 100 
               
               
                  6.6 ± 0.1 
                 13.433 ± 0.207  
                 46 
               
               
                 11.8 ± 0.1 
                 7.481 ± 0.064 
                 55 
               
               
                 12.1 ± 0.1 
                 7.315 ± 0.061 
                 30 
               
               
                 13.2 ± 0.1 
                 6.718 ± 0.051 
                 25 
               
               
                 17.8 ± 0.1 
                 4.983 ± 0.028 
                 21 
               
               
                 20.1 ± 0.1 
                 4.422 ± 0.022 
                 25 
               
               
                 22.2 ± 0.1 
                 4.013 ± 0.018 
                 34 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 6 has an XRPD pattern with peaks at the positions listed in Table 76 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 76 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.3 ± 0.1 
                 26.454 ± 0.816  
                 100 
               
               
                  6.6 ± 0.1 
                 13.433 ± 0.207  
                 46 
               
               
                  8.8 ± 0.1 
                 10.015 ± 0.114  
                 11 
               
               
                 11.3 ± 0.1 
                 7.817 ± 0.069 
                 14 
               
               
                 11.8 ± 0.1 
                 7.481 ± 0.064 
                 55 
               
               
                 12.1 ± 0.1 
                 7.315 ± 0.061 
                 30 
               
               
                 12.5 ± 0.1 
                 7.087 ± 0.057 
                 8 
               
               
                 13.2 ± 0.1 
                 6.718 ± 0.051 
                 25 
               
               
                 14.6 ± 0.1 
                 6.084 ± 0.042 
                 5 
               
               
                 15.2 ± 0.1 
                 5.844 ± 0.039 
                 11 
               
               
                 15.3 ± 0.1 
                 5.776 ± 0.038 
                 10 
               
               
                 15.6 ± 0.1 
                 5.699 ± 0.037 
                 16 
               
               
                 16.0 ± 0.1 
                 5.529 ± 0.034 
                 6 
               
               
                 16.5 ± 0.1 
                 5.379 ± 0.033 
                 10 
               
               
                 17.3 ± 0.1 
                 5.129 ± 0.030 
                 6 
               
               
                 17.8 ± 0.1 
                 4.983 ± 0.028 
                 21 
               
               
                 18.3 ± 0.1 
                 4.853 ± 0.026 
                 8 
               
               
                 18.8 ± 0.1 
                 4.715 ± 0.025 
                 15 
               
               
                 20.1 ± 0.1 
                 4.422 ± 0.022 
                 25 
               
               
                 20.8 ± 0.1 
                 4.271 ± 0.020 
                 16 
               
               
                 21.3 ± 0.1 
                 4.175 ± 0.019 
                 15 
               
               
                 21.6 ± 0.1 
                 4.118 ± 0.019 
                 13 
               
               
                 22.2 ± 0.1 
                 4.013 ± 0.018 
                 34 
               
               
                 22.7 ± 0.1 
                 3.919 ± 0.017 
                 8 
               
               
                 23.8 ± 0.1 
                 3.743 ± 0.016 
                 15 
               
               
                 24.2 ± 0.1 
                 3.679 ± 0.015 
                 10 
               
               
                 24.6 ± 0.1 
                 3.626 ± 0.015 
                 9 
               
               
                 25.0 ± 0.1 
                 3.562 ± 0.014 
                 21 
               
               
                 25.8 ± 0.1 
                 3.460 ± 0.013 
                 11 
               
               
                 26.7 ± 0.1 
                 3.338 ± 0.012 
                 25 
               
               
                 27.5 ± 0.1 
                 3.248 ± 0.012 
                 15 
               
               
                 28.4 ± 0.1 
                 3.144 ± 0.011 
                 14 
               
               
                 29.5 ± 0.1 
                 3.025 ± 0.010 
                 7 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 6 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 51   h.    
     In an embodiment, Form 6 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 99 . 
     In an embodiment, there is provided crystalline Form 7 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     Form 7 may be characterised as having an XRPD pattern with peaks at 4.1 and 6.0 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 11.8 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 16.6, 21.2 and 23.5 °2θ±0.2°θ. 
     In an embodiment, Form 7 has an XRPD pattern with peaks at the positions listed in Table 77 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 77 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 4.1 ± 0.1 
                 21.604 ± 0.541 
                 100 
               
               
                 6.0 ± 0.1 
                 14.633 ± 0.246 
                 46 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 7 has an XRPD pattern with peaks at the positions listed in Table 78 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 78 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.1 ± 0.1 
                 21.604 ± 0.541  
                 100 
               
               
                  6.0 ± 0.1 
                 14.633 ± 0.246  
                 46 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 97 
               
               
                 16.6 ± 0.1 
                 5.341 ± 0.032 
                 76 
               
               
                 21.2 ± 0.1 
                 4.199 ± 0.020 
                 77 
               
               
                 23.5 ± 0.1 
                 3.786 ± 0.016 
                 80 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 7 has an XRPD pattern with peaks at the positions listed in Table 79 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 79 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.1 ± 0.1 
                 21.604 ± 0.541  
                 100 
               
               
                  6.0 ± 0.1 
                 14.633 ± 0.246  
                 46 
               
               
                  8.4 ± 0.1 
                 10.477 ± 0.125  
                 37 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 97 
               
               
                 15.5 ± 0.1 
                 5.732 ± 0.037 
                 41 
               
               
                 16.6 ± 0.1 
                 5.341 ± 0.032 
                 76 
               
               
                 17.5 ± 0.1 
                 5.068 ± 0.029 
                 46 
               
               
                 20.4 ± 0.1 
                 4.351 ± 0.021 
                 63 
               
               
                 21.2 ± 0.1 
                 4.199 ± 0.020 
                 77 
               
               
                 22.6 ± 0.1 
                 3.940 ± 0.017 
                 58 
               
               
                 23.5 ± 0.1 
                 3.786 ± 0.016 
                 80 
               
               
                 24.8 ± 0.1 
                 3.592 ± 0.014 
                 54 
               
               
                 27.1 ± 0.1 
                 3.290 ± 0.012 
                 51 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 7 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 51   i.    
     In an embodiment, Form 7 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 100 . 
     In an embodiment, there is provided crystalline Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate. 
     Form 8 may be characterised as having an XRPD pattern with peaks at 11.7, 12.2, 15.2 and 16.6 °2θ±0.2°2θ. The XRPD pattern may have a further peak at 18.1 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 22.8 and 26.1 °2θ±0.2°θ. 
     In an embodiment, Form 8 has an XRPD pattern with peaks at the positions listed in Table 80 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 80 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 11.7 ± 0.1 
                 7.557 ± 0.065 
                 21 
               
               
                 12.2 ± 0.1 
                 7.225 ± 0.059 
                 14 
               
               
                 15.2 ± 0.1 
                 5.833 ± 0.038 
                 30 
               
               
                 16.6 ± 0.1 
                 5.341 ± 0.032 
                 80 
               
               
                 18.1 ± 0.1 
                 4.901 ± 0.027 
                 100 
               
               
                 22.8 ± 0.1 
                 3.899 ± 0.017 
                 41 
               
               
                 26.1 ± 0.1 
                 3.417 ± 0.013 
                 61 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 8 has an XRPD pattern with peaks at the positions listed in Table 81 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 81 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.4 ± 0.1 
                 13.746 ± 0.217  
                 9 
               
               
                 11.7 ± 0.1 
                 7.557 ± 0.065 
                 21 
               
               
                 12.2 ± 0.1 
                 7.225 ± 0.059 
                 14 
               
               
                 15.2 ± 0.1 
                 5.833 ± 0.038 
                 30 
               
               
                 16.6 ± 0.1 
                 5.341 ± 0.032 
                 80 
               
               
                 18.1 ± 0.1 
                 4.901 ± 0.027 
                 100 
               
               
                 19.0 ± 0.1 
                 4.678 ± 0.025 
                 11 
               
               
                 19.3 ± 0.1 
                 4.599 ± 0.024 
                 14 
               
               
                 19.8 ± 0.1 
                 4.489 ± 0.023 
                 23 
               
               
                 20.6 ± 0.1 
                 4.320 ± 0.021 
                 9 
               
               
                 20.8 ± 0.1 
                 4.271 ± 0.020 
                 8 
               
               
                 21.3 ± 0.1 
                 4.175 ± 0.019 
                 28 
               
               
                 21.7 ± 0.1 
                 4.096 ± 0.019 
                 22 
               
               
                 22.4 ± 0.1 
                 3.966 ± 0.018 
                 7 
               
               
                 22.8 ± 0.1 
                 3.899 ± 0.017 
                 41 
               
               
                 23.5 ± 0.1 
                 3.786 ± 0.016 
                 25 
               
               
                 23.9 ± 0.1 
                 3.729 ± 0.015 
                 38 
               
               
                 24.6 ± 0.1 
                 3.626 ± 0.015 
                 28 
               
               
                 24.9 ± 0.1 
                 3.570 ± 0.014 
                 9 
               
               
                 25.3 ± 0.1 
                 3.520 ± 0.014 
                 33 
               
               
                 26.1 ± 0.1 
                 3.417 ± 0.013 
                 61 
               
               
                 26.5 ± 0.1 
                 3.364 ± 0.013 
                 21 
               
               
                 27.6 ± 0.1 
                 3.234 ± 0.012 
                 13 
               
               
                 28.0 ± 0.1 
                 3.190 ± 0.011 
                 17 
               
               
                 29.2 ± 0.1 
                 3.062 ± 0.010 
                 7 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 52 . 
     In an embodiment, Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate is characterised as having an XRPD pattern as shown in  FIG. 101 . 
     Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate may also be characterised by having a DSC thermogram as shown in  FIG. 58 . 
     According to another aspect of the present invention, there is provided the gentisic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 18.2 and 18.6 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 12.9 and 14.0 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 17.1 and 21.6 °2θ±0.2°θ. The XRPD pattern may have yet further peaks at 24.8 and 25.7 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 82 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 82 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 18.2 ± 0.1 
                 4.877 ± 0.027 
                 85 
               
               
                 18.6 ± 0.1 
                 4.760 ± 0.025 
                 93 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 83 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 83 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 12.9 ± 0.1 
                 6.842 ± 0.053 
                 23 
               
               
                 14.0 ± 0.1 
                 6.317 ± 0.045 
                 19 
               
               
                 17.1 ± 0.1 
                 5.192 ± 0.030 
                 99 
               
               
                 18.2 ± 0.1 
                 4.877 ± 0.027 
                 85 
               
               
                 18.6 ± 0.1 
                 4.760 ± 0.025 
                 93 
               
               
                 21.6 ± 0.1 
                 4.118 ± 0.019 
                 53 
               
               
                 22.2 ± 0.1 
                 4.008 ± 0.018 
                 49 
               
               
                 22.5 ± 0.1 
                 3.945 ± 0.017 
                 45 
               
               
                 24.8 ± 0.1 
                 3.583 ± 0.014 
                 85 
               
               
                 25.7 ± 0.1 
                 3.468 ± 0.013 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 84 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 84 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.8 ± 0.1 
                 18.372 ± 0.390  
                 12 
               
               
                  9.8 ± 0.1 
                 9.035 ± 0.093 
                 12 
               
               
                 12.9 ± 0.1 
                 6.842 ± 0.053 
                 23 
               
               
                 13.4 ± 0.1 
                 6.613 ± 0.050 
                 11 
               
               
                 14.0 ± 0.1 
                 6.317 ± 0.045 
                 19 
               
               
                 14.6 ± 0.1 
                 6.059 ± 0.042 
                 31 
               
               
                 15.2 ± 0.1 
                 5.810 ± 0.038 
                 20 
               
               
                 16.7 ± 0.1 
                 5.312 ± 0.032 
                 10 
               
               
                 17.1 ± 0.1 
                 5.192 ± 0.030 
                 99 
               
               
                 18.2 ± 0.1 
                 4.877 ± 0.027 
                 85 
               
               
                 18.6 ± 0.1 
                 4.760 ± 0.025 
                 93 
               
               
                 20.2 ± 0.1 
                 4.390 ± 0.022 
                 11 
               
               
                 20.7 ± 0.1 
                 4.295 ± 0.021 
                 21 
               
               
                 21.6 ± 0.1 
                 4.118 ± 0.019 
                 53 
               
               
                 22.2 ± 0.1 
                 4.008 ± 0.018 
                 49 
               
               
                 22.5 ± 0.1 
                 3.945 ± 0.017 
                 45 
               
               
                 23.6 ± 0.1 
                 3.762 ± 0.016 
                 22 
               
               
                 23.9 ± 0.1 
                 3.729 ± 0.015 
                 17 
               
               
                 24.8 ± 0.1 
                 3.583 ± 0.014 
                 85 
               
               
                 25.7 ± 0.1 
                 3.468 ± 0.013 
                 100 
               
               
                 26.0 ± 0.1 
                 3.428 ± 0.013 
                 51 
               
               
                 26.4 ± 0.1 
                 3.371 ± 0.013 
                 29 
               
               
                 26.8 ± 0.1 
                 3.327 ± 0.012 
                 30 
               
               
                 28.2 ± 0.1 
                 3.170 ± 0.011 
                 52 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate is characterised as having an XRPD pattern as shown in  FIG. 32   a . In another embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate is characterised as having an XRPD pattern as shown in  FIG. 32   b.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate is characterised as having an XRPD pattern as shown in  FIG. 102 . 
     In an embodiment, there is provided crystalline Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate. 
     Form 2 may be characterised as having an XRPD pattern with a peak at 3.9 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 19.3 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 12.9 and 13.7 °2θ±0.2°θ. The XRPD pattern may have yet further peaks at 15.4 and 16.6 °2θ±0.2°θ. The XRPD pattern may have still yet further peaks at 25.5 and 26.1 °2θ±0.2°θ. 
     In an embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 85 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 85 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  3.9 ± 0.1 
                 22.541 ± 0.590 
                 56 
               
               
                 19.3 ± 0.1 
                  4.604 ± 0.024 
                 36 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 86 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 86 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.9 ± 0.1 
                 22.541 ± 0.590  
                 56 
               
               
                 12.9 ± 0.1 
                 6.852 ± 0.053 
                 38 
               
               
                 13.7 ± 0.1 
                 6.454 ± 0.047 
                 18 
               
               
                 15.4 ± 0.1 
                 5.769 ± 0.038 
                 31 
               
               
                 16.6 ± 0.1 
                 5.341 ± 0.032 
                 36 
               
               
                 19.3 ± 0.1 
                 4.604 ± 0.024 
                 36 
               
               
                 21.8 ± 0.1 
                 4.084 ± 0.019 
                 45 
               
               
                 22.4 ± 0.1 
                 3.976 ± 0.018 
                 53 
               
               
                 25.5 ± 0.1 
                 3.496 ± 0.014 
                 75 
               
               
                 26.1 ± 0.1 
                 3.417 ± 0.013 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 87 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 87 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.9 ± 0.1 
                 22.541 ± 0.590  
                 56 
               
               
                 12.9 ± 0.1 
                 6.852 ± 0.053 
                 38 
               
               
                 13.7 ± 0.1 
                 6.454 ± 0.047 
                 18 
               
               
                 15.4 ± 0.1 
                 5.769 ± 0.038 
                 31 
               
               
                 16.6 ± 0.1 
                 5.341 ± 0.032 
                 36 
               
               
                 17.1 ± 0.1 
                 5.179 ± 0.030 
                 22 
               
               
                 17.8 ± 0.1 
                 4.994 ± 0.028 
                 21 
               
               
                 18.8 ± 0.1 
                 4.730 ± 0.025 
                 20 
               
               
                 19.3 ± 0.1 
                 4.604 ± 0.024 
                 36 
               
               
                 20.7 ± 0.1 
                 4.295 ± 0.021 
                 14 
               
               
                 21.8 ± 0.1 
                 4.084 ± 0.019 
                 45 
               
               
                 22.4 ± 0.1 
                 3.976 ± 0.018 
                 53 
               
               
                 22.9 ± 0.1 
                 3.880 ± 0.017 
                 29 
               
               
                 25.0 ± 0.1 
                 3.556 ± 0.014 
                 45 
               
               
                 25.5 ± 0.1 
                 3.496 ± 0.014 
                 75 
               
               
                 26.1 ± 0.1 
                 3.417 ± 0.013 
                 100 
               
               
                 27.7 ± 0.1 
                 3.223 ± 0.011 
                 30 
               
               
                 28.5 ± 0.1 
                 3.130 ± 0.011 
                 24 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate is characterised as having an XRPD pattern as shown in  FIG. 32   c.    
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate is characterised as having an XRPD pattern as shown in  FIG. 103 . 
     In another embodiment, Form 2 of the gentisate salt is characterised as being in the form of a solvate of ethyl acetate. The number of moles of ethyl acetate per mole of Form 2 may range from about 0.4 to about 1.0. Typically, the number of moles ranges from about 0.5 to about 0.9, more typically from about 0.6 to about 0.8. In an embodiment, there is 0.7 mole of ethyl acetate per 1 mole of Form 2. 
     According to another aspect of the present invention, there is provided the citric acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 10.6 and 13.7 °2θ±0.2°2θ. The XRPD pattern may have a further peak at 8.9 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 12.3 °2θ±0.2°θ. The XRPD pattern may have yet further peaks at 15.6 and 15.9 °2θ±0.2°θ. The XRPD pattern may have still yet further peaks at 23.2 and 26.4 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 88 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 88 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  8.9 ± 0.1 
                 9.914 ± 0.112 
                 18 
               
               
                 10.6 ± 0.1 
                 8.378 ± 0.080 
                 37 
               
               
                 13.7 ± 0.1 
                 6.473 ± 0.047 
                 38 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 89 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 89 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  8.9 ± 0.1 
                 9.914 ± 0.112 
                 18 
               
               
                 10.6 ± 0.1 
                 8.378 ± 0.080 
                 37 
               
               
                 12.3 ± 0.1 
                 7.185 ± 0.059 
                 52 
               
               
                 13.7 ± 0.1 
                 6.473 ± 0.047 
                 38 
               
               
                 15.6 ± 0.1 
                 5.695 ± 0.037 
                 73 
               
               
                 15.9 ± 0.1 
                 5.581 ± 0.035 
                 72 
               
               
                 23.2 ± 0.1 
                 3.828 ± 0.016 
                 65 
               
               
                 26.4 ± 0.1 
                 3.381 ± 0.013 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 90 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 90 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  8.9 ± 0.1 
                 9.914 ± 0.112 
                 18 
               
               
                 10.6 ± 0.1 
                 8.378 ± 0.080 
                 37 
               
               
                 12.3 ± 0.1 
                 7.185 ± 0.059 
                 52 
               
               
                 13.0 ± 0.1 
                 6.810 ± 0.053 
                 26 
               
               
                 13.7 ± 0.1 
                 6.473 ± 0.047 
                 38 
               
               
                 14.7 ± 0.1 
                 6.018 ± 0.041 
                 21 
               
               
                 15.6 ± 0.1 
                 5.695 ± 0.037 
                 73 
               
               
                 15.9 ± 0.1 
                 5.581 ± 0.035 
                 72 
               
               
                 17.0 ± 0.1 
                 5.204 ± 0.030 
                 22 
               
               
                 18.6 ± 0.1 
                 4.760 ± 0.025 
                 29 
               
               
                 19.4 ± 0.1 
                 4.585 ± 0.024 
                 43 
               
               
                 20.8 ± 0.1 
                 4.271 ± 0.020 
                 43 
               
               
                 21.3 ± 0.1 
                 4.175 ± 0.019 
                 38 
               
               
                 22.3 ± 0.1 
                 3.990 ± 0.018 
                 35 
               
               
                 22.6 ± 0.1 
                 3.934 ± 0.017 
                 36 
               
               
                 23.2 ± 0.1 
                 3.828 ± 0.016 
                 65 
               
               
                 24.0 ± 0.1 
                 3.702 ± 0.015 
                 51 
               
               
                 24.6 ± 0.1 
                 3.613 ± 0.014 
                 54 
               
               
                 26.4 ± 0.1 
                 3.381 ± 0.013 
                 100 
               
               
                 28.6 ± 0.1 
                 3.117 ± 0.011 
                 30 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate is characterised as having an XRPD pattern as shown in  FIG. 27   a . In another embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate is characterised as having an XRPD pattern as shown in  FIG. 27   c.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate is characterised as having an XRPD pattern as shown in  FIG. 104 . 
     In another embodiment, there is provided crystalline Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate. 
     Form 2 may be characterised as having an XRPD pattern with peaks at 6.1 and 7.4 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 13.4 and 14.7 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 15.7 °2θ±0.2°θ. 
     In an embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 91 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 91 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 6.1 ± 0.1 
                 14.561 ± 0.244 
                 25 
               
               
                 7.4 ± 0.1 
                 12.011 ± 0.165 
                 100 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 100 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 100 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.1 ± 0.1 
                 14.561 ± 0.244  
                 25 
               
               
                  7.4 ± 0.1 
                 12.011 ± 0.165  
                 100 
               
               
                 13.4 ± 0.1 
                 6.583 ± 0.049 
                 27 
               
               
                 14.7 ± 0.1 
                 6.010 ± 0.041 
                 29 
               
               
                 15.7 ± 0.1 
                 5.634 ± 0.036 
                 35 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 2 has an XRPD pattern with peaks at the positions listed in Table 101 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 101 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.1 ± 0.1 
                 14.561 ± 0.244  
                 25 
               
               
                  7.4 ± 0.1 
                 12.011 ± 0.165  
                 100 
               
               
                  8.0 ± 0.1 
                 10.983 ± 0.138  
                 5 
               
               
                 10.8 ± 0.1 
                 8.162 ± 0.076 
                 9 
               
               
                 12.3 ± 0.1 
                 7.208 ± 0.059 
                 10 
               
               
                 13.4 ± 0.1 
                 6.583 ± 0.049 
                 27 
               
               
                 14.7 ± 0.1 
                 6.010 ± 0.041 
                 29 
               
               
                 15.7 ± 0.1 
                 5.634 ± 0.036 
                 35 
               
               
                 16.0 ± 0.1 
                 5.539 ± 0.035 
                 18 
               
               
                 17.6 ± 0.1 
                 5.042 ± 0.029 
                 9 
               
               
                 18.2 ± 0.1 
                 4.861 ± 0.027 
                 6 
               
               
                 19.0 ± 0.1 
                 4.664 ± 0.024 
                 4 
               
               
                 19.9 ± 0.1 
                 4.468 ± 0.022 
                 7 
               
               
                 20.8 ± 0.1 
                 4.271 ± 0.020 
                 13 
               
               
                 21.6 ± 0.1 
                 4.107 ± 0.019 
                 19 
               
               
                 23.2 ± 0.1 
                 3.839 ± 0.016 
                 20 
               
               
                 23.6 ± 0.1 
                 3.776 ± 0.016 
                 30 
               
               
                 24.4 ± 0.1 
                 3.648 ± 0.015 
                 31 
               
               
                 26.0 ± 0.1 
                 3.432 ± 0.013 
                 18 
               
               
                 27.4 ± 0.1 
                 3.259 ± 0.012 
                 18 
               
               
                 28.5 ± 0.1 
                 3.134 ± 0.011 
                 6 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate is characterised as having an XRPD pattern as shown in  FIG. 27   b.    
     In an embodiment, Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate is characterised as having an XRPD pattern as shown in  FIG. 105 . 
     Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate may also be characterised by having a DSC thermogram as shown in  FIG. 31 . 
     According to another aspect of the present invention, there is provided the lactic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione lactate. In another embodiment, there is provided crystalline (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione lactate. Crystalline (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione lactate may be characterised by having an XRPD pattern as shown in  FIG. 45 . 
     According to another aspect of the present invention, there is provided the L-malic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-malate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-malate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 8.0, 9.0, 10.7, 12.0, 12.6 and 13.9 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 15.6 and 20.2 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 20.8 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 102 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 102 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  8.0 ± 0.1 
                 10.983 ± 0.138  
                 37 
               
               
                  9.0 ± 0.1 
                 9.848 ± 0.111 
                 32 
               
               
                 10.7 ± 0.1 
                 8.276 ± 0.078 
                 30 
               
               
                 12.0 ± 0.1 
                 7.351 ± 0.061 
                 27 
               
               
                 12.6 ± 0.1 
                 7.053 ± 0.056 
                 92 
               
               
                 13.9 ± 0.1 
                 6.385 ± 0.046 
                 63 
               
               
                 15.6 ± 0.1 
                 5.677 ± 0.036 
                 100 
               
               
                 20.2 ± 0.1 
                 4.390 ± 0.022 
                 79 
               
               
                 20.8 ± 0.1 
                 4.277 ± 0.020 
                 46 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 103 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 103 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.5 ± 0.1 
                 19.464 ± 0.438  
                 20 
               
               
                  8.0 ± 0.1 
                 10.983 ± 0.138  
                 37 
               
               
                  9.0 ± 0.1 
                 9.848 ± 0.111 
                 32 
               
               
                  9.8 ± 0.1 
                 9.007 ± 0.092 
                 6 
               
               
                 10.7 ± 0.1 
                 8.276 ± 0.078 
                 30 
               
               
                 12.0 ± 0.1 
                 7.351 ± 0.061 
                 27 
               
               
                 12.6 ± 0.1 
                 7.053 ± 0.056 
                 92 
               
               
                 13.9 ± 0.1 
                 6.385 ± 0.046 
                 63 
               
               
                 15.6 ± 0.1 
                 5.677 ± 0.036 
                 100 
               
               
                 15.8 ± 0.1 
                 5.591 ± 0.035 
                 59 
               
               
                 16.1 ± 0.1 
                 5.509 ± 0.034 
                 27 
               
               
                 16.5 ± 0.1 
                 5.369 ± 0.032 
                 19 
               
               
                 17.9 ± 0.1 
                 4.966 ± 0.028 
                 14 
               
               
                 19.5 ± 0.1 
                 4.550 ± 0.023 
                 30 
               
               
                 19.8 ± 0.1 
                 4.482 ± 0.023 
                 22 
               
               
                 20.2 ± 0.1 
                 4.390 ± 0.022 
                 79 
               
               
                 20.8 ± 0.1 
                 4.277 ± 0.020 
                 46 
               
               
                 21.6 ± 0.1 
                 4.124 ± 0.019 
                 24 
               
               
                 22.4 ± 0.1 
                 3.960 ± 0.017 
                 30 
               
               
                 23.4 ± 0.1 
                 3.805 ± 0.016 
                 22 
               
               
                 23.7 ± 0.1 
                 3.753 ± 0.016 
                 26 
               
               
                 24.2 ± 0.1 
                 3.670 ± 0.015 
                 79 
               
               
                 24.5 ± 0.1 
                 3.631 ± 0.015 
                 92 
               
               
                 25.0 ± 0.1 
                 3.562 ± 0.014 
                 99 
               
               
                 25.5 ± 0.1 
                 3.492 ± 0.014 
                 26 
               
               
                 26.0 ± 0.1 
                 3.425 ± 0.013 
                 35 
               
               
                 26.8 ± 0.1 
                 3.330 ± 0.012 
                 32 
               
               
                 27.1 ± 0.1 
                 3.294 ± 0.012 
                 30 
               
               
                 27.6 ± 0.1 
                 3.227 ± 0.011 
                 16 
               
               
                 28.4 ± 0.1 
                 3.147 ± 0.011 
                 26 
               
               
                 29.8 ± 0.1 
                 2.995 ± 0.010 
                 15 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malate is characterised as having an XRPD pattern as shown in  FIG. 47   a . In another embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malate is characterised as having an XRPD pattern as shown in  FIG. 47   b.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malate is characterised as having an XRPD pattern as shown in  FIG. 106 . 
     According to another aspect of the present invention, there is provided the glycolic acid salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glycolate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glycolate. 
     Form 1 may be characterised as having an XRPD pattern with peaks at 5.2, 11.8, and 12.9 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 14.8 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 15.2, 16.7, 17.1, 17.6 and 18.5 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 104 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 104 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.2 ± 0.1 
                 17.093 ± 0.337  
                 43 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 95 
               
               
                 12.9 ± 0.1 
                 6.873 ± 0.054 
                 62 
               
               
                 14.8 ± 0.1 
                 5.986 ± 0.040 
                 23 
               
               
                 15.2 ± 0.1 
                 5.833 ± 0.038 
                 28 
               
               
                 16.7 ± 0.1 
                 5.321 ± 0.032 
                 66 
               
               
                 17.1 ± 0.1 
                 5.182 ± 0.030 
                 68 
               
               
                 17.6 ± 0.1 
                 5.051 ± 0.029 
                 43 
               
               
                 18.5 ± 0.1 
                 4.791 ± 0.026 
                 49 
               
               
                 21.6 ± 0.1 
                 4.124 ± 0.019 
                 44 
               
               
                 22.9 ± 0.1 
                 3.879 ± 0.017 
                 32 
               
               
                 23.6 ± 0.1 
                 3.762 ± 0.016 
                 40 
               
               
                 24.9 ± 0.1 
                 3.579 ± 0.014 
                 88 
               
               
                 25.3 ± 0.1 
                 3.516 ± 0.014 
                 100 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 105 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 105 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  5.2 ± 0.1 
                 17.093 ± 0.337  
                 43 
               
               
                 11.8 ± 0.1 
                 7.519 ± 0.064 
                 95 
               
               
                 12.9 ± 0.1 
                 6.873 ± 0.054 
                 62 
               
               
                 14.8 ± 0.1 
                 5.986 ± 0.040 
                 23 
               
               
                 15.2 ± 0.1 
                 5.833 ± 0.038 
                 28 
               
               
                 15.5 ± 0.1 
                 5.710 ± 0.037 
                 9 
               
               
                 16.7 ± 0.1 
                 5.321 ± 0.032 
                 66 
               
               
                 17.1 ± 0.1 
                 5.182 ± 0.030 
                 68 
               
               
                 17.6 ± 0.1 
                 5.051 ± 0.029 
                 43 
               
               
                 18.5 ± 0.1 
                 4.791 ± 0.026 
                 49 
               
               
                 18.7 ± 0.1 
                 4.738 ± 0.025 
                 29 
               
               
                 20.1 ± 0.1 
                 4.409 ± 0.022 
                 10 
               
               
                 21.1 ± 0.1 
                 4.205 ± 0.020 
                 19 
               
               
                 21.6 ± 0.1 
                 4.124 ± 0.019 
                 44 
               
               
                 21.8 ± 0.1 
                 4.079 ± 0.019 
                 13 
               
               
                 22.9 ± 0.1 
                 3.879 ± 0.017 
                 32 
               
               
                 23.4 ± 0.1 
                 3.805 ± 0.016 
                 13 
               
               
                 23.6 ± 0.1 
                 3.762 ± 0.016 
                 40 
               
               
                 24.9 ± 0.1 
                 3.579 ± 0.014 
                 88 
               
               
                 25.3 ± 0.1 
                 3.516 ± 0.014 
                 100 
               
               
                 26.2 ± 0.1 
                 3.401 ± 0.013 
                 27 
               
               
                 26.4 ± 0.1 
                 3.379 ± 0.013 
                 28 
               
               
                 27.2 ± 0.1 
                 3.276 ± 0.012 
                 18 
               
               
                 28.2 ± 0.1 
                 3.163 ± 0.011 
                 47 
               
               
                 28.4 ± 0.1 
                 3.141 ± 0.011 
                 63 
               
               
                 29.9 ± 0.1 
                 2.992 ± 0.010 
                 22 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glycolate is characterised as having an XRPD pattern as shown in  FIG. 37   a . In another embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glycolate is characterised as having an XRPD pattern as shown in  FIG. 37   b.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glycolate is characterised as having an XRPD pattern as shown in  FIG. 107 . 
     Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glycolate may also be characterised by having a DSC thermogram as shown in  FIG. 39 . 
     According to another aspect of the present invention, there is provided (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. 
     In an embodiment, there is provided crystalline Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. 
     Form 1 may be characterised as having an XRPD pattern with a peak at 8.9 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 17.7 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 11.0, 12.4, 12.7 and 13.7 °2θ±0.2°θ. The XRPD pattern may have yet further peaks at 16.0, 17.0 and 22.1 °2θ±0.2°θ. 
     In an embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 106 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 106 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  8.9 ± 0.1 
                 9.947 ± 0.113 
                 11 
               
               
                 17.7 ± 0.1 
                 5.000 ± 0.028 
                 53 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 107 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 107 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  8.9 ± 0.1 
                 9.947 ± 0.113 
                 11 
               
               
                 11.0 ± 0.1 
                 8.007 ± 0.073 
                 28 
               
               
                 12.4 ± 0.1 
                 7.156 ± 0.058 
                 14 
               
               
                 12.7 ± 0.1 
                 6.970 ± 0.055 
                 24 
               
               
                 13.7 ± 0.1 
                 6.483 ± 0.048 
                 26 
               
               
                 16.0 ± 0.1 
                 5.550 ± 0.035 
                 59 
               
               
                 17.0 ± 0.1 
                 5.210 ± 0.031 
                 38 
               
               
                 17.7 ± 0.1 
                 5.000 ± 0.028 
                 53 
               
               
                 22.1 ± 0.1 
                 4.019 ± 0.018 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 1 has an XRPD pattern with peaks at the positions listed in Table 108 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 108 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  7.3 ± 0.1 
                 12.160 ± 0.169  
                 7 
               
               
                  8.9 ± 0.1 
                 9.947 ± 0.113 
                 11 
               
               
                 11.0 ± 0.1 
                 8.007 ± 0.073 
                 28 
               
               
                 12.4 ± 0.1 
                 7.156 ± 0.058 
                 14 
               
               
                 12.7 ± 0.1 
                 6.970 ± 0.055 
                 24 
               
               
                 13.4 ± 0.1 
                 6.583 ± 0.049 
                 14 
               
               
                 13.7 ± 0.1 
                 6.483 ± 0.048 
                 26 
               
               
                 14.6 ± 0.1 
                 6.084 ± 0.042 
                 4 
               
               
                 15.2 ± 0.1 
                 5.844 ± 0.039 
                 5 
               
               
                 16.0 ± 0.1 
                 5.550 ± 0.035 
                 59 
               
               
                 17.0 ± 0.1 
                 5.210 ± 0.031 
                 38 
               
               
                 17.7 ± 0.1 
                 5.000 ± 0.028 
                 53 
               
               
                 19.1 ± 0.1 
                 4.649 ± 0.024 
                 12 
               
               
                 20.3 ± 0.1 
                 4.370 ± 0.021 
                 6 
               
               
                 21.5 ± 0.1 
                 4.129 ± 0.019 
                 28 
               
               
                 22.1 ± 0.1 
                 4.019 ± 0.018 
                 100 
               
               
                 22.7 ± 0.1 
                 3.919 ± 0.017 
                 19 
               
               
                 23.4 ± 0.1 
                 3.795 ± 0.016 
                 22 
               
               
                 23.6 ± 0.1 
                 3.762 ± 0.016 
                 21 
               
               
                 24.0 ± 0.1 
                 3.706 ± 0.015 
                 10 
               
               
                 24.5 ± 0.1 
                 3.631 ± 0.015 
                 29 
               
               
                 24.9 ± 0.1 
                 3.570 ± 0.014 
                 38 
               
               
                 26.4 ± 0.1 
                 3.375 ± 0.013 
                 15 
               
               
                 27.1 ± 0.1 
                 3.290 ± 0.012 
                 9 
               
               
                 27.6 ± 0.1 
                 3.238 ± 0.012 
                 27 
               
               
                 28.2 ± 0.1 
                 3.163 ± 0.011 
                 4 
               
               
                 28.9 ± 0.1 
                 3.093 ± 0.011 
                 10 
               
               
                 29.3 ± 0.1 
                 3.049 ± 0.010 
                 30 
               
               
                 29.7 ± 0.1 
                 3.004 ± 0.010 
                 8 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 63   a . In another embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 63   h.    
     In an embodiment, Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 108 . 
     Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate may also be characterised by having a DSC thermogram as shown in  FIG. 65 . 
     In an embodiment, there is provided a crystal modification of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. This crystal modification is hereinafter referred to as crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. 
     Crystal modification X may be characterised as having an XRPD pattern with peaks at 12.7 and 15.8 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 21.6 and 24.1 °2θ±0.2°θ. 
     In an embodiment, crystal modification X has an XRPD pattern with peaks at the positions listed in Table 109 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 109 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 12.7 ± 0.1 
                 6.981 ± 0.055 
                 24 
               
               
                 15.8 ± 0.1 
                 5.623 ± 0.036 
                 25 
               
               
                 21.6 ± 0.1 
                 4.107 ± 0.019 
                 71 
               
               
                 24.1 ± 0.1 
                 3.696 ± 0.015 
                 100 
               
               
                   
               
            
           
         
       
     
     In another embodiment, crystal modification X has an XRPD pattern with peaks at the positions listed in Table 110 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 110 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 10.9 ± 0.1 
                 8.102 ± 0.075 
                 7 
               
               
                 12.3 ± 0.1 
                 7.208 ± 0.059 
                 10 
               
               
                 12.7 ± 0.1 
                 6.981 ± 0.055 
                 24 
               
               
                 13.7 ± 0.1 
                 6.454 ± 0.047 
                 13 
               
               
                 15.8 ± 0.1 
                 5.623 ± 0.036 
                 25 
               
               
                 17.1 ± 0.1 
                 5.192 ± 0.030 
                 6 
               
               
                 19.0 ± 0.1 
                 4.671 ± 0.024 
                 10 
               
               
                 21.6 ± 0.1 
                 4.107 ± 0.019 
                 71 
               
               
                 22.0 ± 0.1 
                 4.033 ± 0.018 
                 22 
               
               
                 22.8 ± 0.1 
                 3.900 ± 0.017 
                 31 
               
               
                 24.1 ± 0.1 
                 3.696 ± 0.015 
                 100 
               
               
                 25.6 ± 0.1 
                 3.480 ± 0.013 
                 12 
               
               
                 26.3 ± 0.1 
                 3.386 ± 0.013 
                 19 
               
               
                 27.5 ± 0.1 
                 3.246 ± 0.012 
                 11 
               
               
                 28.3 ± 0.1 
                 3.151 ± 0.011 
                 22 
               
               
                 29.2 ± 0.1 
                 3.063 ± 0.010 
                 19 
               
               
                   
               
            
           
         
       
     
     In an embodiment, crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 63   d.    
     In another embodiment, crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 109 . 
     In an embodiment, there is provided crystalline Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. 
     Form 3 may be characterised as having an XRPD pattern with a peak at 9.6 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 16.4 °2θ±0.2 °2θ. The XRPD pattern may have a still further peak at 12.8 °2θ±0.2°θ. The XRPD pattern may have yet further peaks at 17.0, 19.1 and 27.1 °2θ±0.2°θ. 
     In an embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 112 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 112 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  9.6 ± 0.1 
                 9.252 ± 0.098 
                 19 
               
               
                 16.4 ± 0.1 
                 5.418 ± 0.033 
                 51 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 113 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 113 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  9.6 ± 0.1 
                 9.252 ± 0.098 
                 19 
               
               
                 12.8 ± 0.1 
                 6.895 ± 0.054 
                 70 
               
               
                 16.4 ± 0.1 
                 5.418 ± 0.033 
                 51 
               
               
                 17.0 ± 0.1 
                 5.204 ± 0.030 
                 42 
               
               
                 19.1 ± 0.1 
                 4.652 ± 0.024 
                 56 
               
               
                 27.1 ± 0.1 
                 3.288 ± 0.012 
                 100 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 3 has an XRPD pattern with peaks at the positions listed in Table 114 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 114 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  9.6 ± 0.1 
                 9.252 ± 0.098 
                 19 
               
               
                 10.0 ± 0.1 
                 8.846 ± 0.089 
                 14 
               
               
                 10.7 ± 0.1 
                 8.284 ± 0.078 
                 15 
               
               
                 12.8 ± 0.1 
                 6.895 ± 0.054 
                 70 
               
               
                 13.4 ± 0.1 
                 6.588 ± 0.049 
                 21 
               
               
                 14.3 ± 0.1 
                 6.203 ± 0.044 
                 27 
               
               
                 15.0 ± 0.1 
                 5.922 ± 0.040 
                 33 
               
               
                 16.4 ± 0.1 
                 5.418 ± 0.033 
                 51 
               
               
                 17.0 ± 0.1 
                 5.204 ± 0.030 
                 42 
               
               
                 18.0 ± 0.1 
                 4.928 ± 0.027 
                 24 
               
               
                 19.1 ± 0.1 
                 4.652 ± 0.024 
                 56 
               
               
                 20.7 ± 0.1 
                 4.295 ± 0.021 
                 33 
               
               
                 22.2 ± 0.1 
                 4.012 ± 0.018 
                 44 
               
               
                 22.7 ± 0.1 
                 3.921 ± 0.017 
                 42 
               
               
                 24.2 ± 0.1 
                 3.684 ± 0.015 
                 55 
               
               
                 26.4 ± 0.1 
                 3.381 ± 0.013 
                 51 
               
               
                 27.1 ± 0.1 
                 3.288 ± 0.012 
                 100 
               
               
                 28.0 ± 0.1 
                 3.182 ± 0.011 
                 39 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 63   f.    
     In an embodiment, Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 110 . 
     In an embodiment, there is provided another crystal modification of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. This crystal modification is hereinafter referred to as crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. 
     Crystal modification Y may be characterised as having an XRPD pattern with peaks at 17.2 and 19.1 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 24.1, 24.6, 27.7 and 29.3 °2θ±0.2°2θ. 
     In an embodiment, crystal modification Y has an XRPD pattern with peaks at the positions listed in Table 115 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 115 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 17.2 ± 0.1 
                 5.167 ± 0.030 
                 16 
               
               
                 19.1 ± 0.1 
                 4.642 ± 0.024 
                 22 
               
               
                 24.1 ± 0.1 
                 3.690 ± 0.015 
                 18 
               
               
                 24.6 ± 0.1 
                 3.625 ± 0.015 
                 16 
               
               
                 27.7 ± 0.1 
                 3.223 ± 0.011 
                 29 
               
               
                 29.3 ± 0.1 
                 3.046 ± 0.010 
                 100 
               
               
                   
               
            
           
         
       
     
     In another embodiment, crystal modification Y has an XRPD pattern with peaks at the positions listed in Table 116 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 116 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 17.2 ± 0.1 
                 5.167 ± 0.030 
                 16 
               
               
                 19.1 ± 0.1 
                 4.642 ± 0.024 
                 22 
               
               
                 22.5 ± 0.1 
                 3.948 ± 0.017 
                 8 
               
               
                 24.1 ± 0.1 
                 3.690 ± 0.015 
                 18 
               
               
                 24.6 ± 0.1 
                 3.625 ± 0.015 
                 16 
               
               
                 26.5 ± 0.1 
                 3.361 ± 0.012 
                 8 
               
               
                 27.7 ± 0.1 
                 3.223 ± 0.011 
                 29 
               
               
                 29.3 ± 0.1 
                 3.046 ± 0.010 
                 100 
               
               
                 29.8 ± 0.1 
                 3.002 ± 0.010 
                 25 
               
               
                   
               
            
           
         
       
     
     In an embodiment, crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 63   g.    
     In another embodiment, crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 111 . 
     In an embodiment, there is provided crystalline Form 6 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. 
     Form 6 may be characterised as having an XRPD pattern with peaks at 6.2 and 12.7 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 15.5, 16.8 and 18.3 °2θ±0.2°2θ. The XRPD pattern may have still further peaks at 21.7, 24.7 and 25.4 °2θ±0.2°θ. 
     In an embodiment, Form 6 has an XRPD pattern with peaks at the positions listed in Table 117 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 117 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.2 ± 0.1 
                 14.210 ± 0.232  
                 12 
               
               
                 12.7 ± 0.1 
                 6.987 ± 0.055 
                 19 
               
               
                 15.5 ± 0.1 
                 5.710 ± 0.037 
                 31 
               
               
                 16.8 ± 0.1 
                 5.274 ± 0.031 
                 66 
               
               
                 18.3 ± 0.1 
                 4.838 ± 0.026 
                 100 
               
               
                 21.7 ± 0.1 
                 4.101 ± 0.019 
                 56 
               
               
                 24.7 ± 0.1 
                 3.609 ± 0.014 
                 71 
               
               
                 25.4 ± 0.1 
                 3.512 ± 0.014 
                 56 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 6 has an XRPD pattern with peaks at the positions listed in Table 118 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 118 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  6.2 ± 0.1 
                 14.210 ± 0.232  
                 12 
               
               
                 12.4 ± 0.1 
                 7.156 ± 0.058 
                 11 
               
               
                 12.7 ± 0.1 
                 6.987 ± 0.055 
                 19 
               
               
                 14.3 ± 0.1 
                 6.211 ± 0.044 
                 5 
               
               
                 15.5 ± 0.1 
                 5.710 ± 0.037 
                 31 
               
               
                 16.8 ± 0.1 
                 5.274 ± 0.031 
                 66 
               
               
                 18.3 ± 0.1 
                 4.838 ± 0.026 
                 100 
               
               
                 18.7 ± 0.1 
                 4.738 ± 0.025 
                 25 
               
               
                 20.0 ± 0.1 
                 4.435 ± 0.022 
                 24 
               
               
                 20.6 ± 0.1 
                 4.314 ± 0.021 
                 15 
               
               
                 21.2 ± 0.1 
                 4.193 ± 0.020 
                 11 
               
               
                 21.7 ± 0.1 
                 4.101 ± 0.019 
                 56 
               
               
                 22.2 ± 0.1 
                 4.003 ± 0.018 
                 13 
               
               
                 23.4 ± 0.1 
                 3.810 ± 0.016 
                 34 
               
               
                 23.6 ± 0.1 
                 3.772 ± 0.016 
                 32 
               
               
                 24.0 ± 0.1 
                 3.702 ± 0.015 
                 24 
               
               
                 24.3 ± 0.1 
                 3.661 ± 0.015 
                 22 
               
               
                 24.7 ± 0.1 
                 3.609 ± 0.014 
                 71 
               
               
                 25.4 ± 0.1 
                 3.512 ± 0.014 
                 56 
               
               
                 27.0 ± 0.1 
                 3.305 ± 0.012 
                 9 
               
               
                 27.7 ± 0.1 
                 3.217 ± 0.011 
                 32 
               
               
                 28.5 ± 0.1 
                 3.128 ± 0.011 
                 9 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 6 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 63   j.    
     In an embodiment, Form 6 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 112 . 
     In an embodiment, there is provided crystalline Form 7 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. 
     Form 7 may be characterised as having an XRPD pattern with a peak at 3.8 °2θ±0.2 °2θ. The XRPD pattern may have a further peak at 17.5 °2θ±0.2°2θ. The XRPD pattern may have still further peaks at 12.8 and 14.7 °2θ±0.2°θ. The XRPD pattern may have a yet further peak at 20.2 °2θ±0.2°θ. 
     In an embodiment, Form 7 has an XRPD pattern with peaks at the positions listed in Table 119 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 119 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.8 ± 0.1 
                 23.131 ± 0.622 
                 100 
               
               
                 17.5 ± 0.1 
                  5.076 ± 0.029 
                 34 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 7 has an XRPD pattern with peaks at the positions listed in Table 120 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 120 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.8 ± 0.1 
                 23.131 ± 0.622  
                 100 
               
               
                 12.8 ± 0.1 
                 6.938 ± 0.055 
                 34 
               
               
                 14.7 ± 0.1 
                 6.034 ± 0.041 
                 53 
               
               
                 17.5 ± 0.1 
                 5.076 ± 0.029 
                 34 
               
               
                 20.2 ± 0.1 
                 4.396 ± 0.022 
                 54 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 7 has an XRPD pattern with peaks at the positions listed in Table 121 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 121 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  3.8 ± 0.1 
                 23.131 ± 0.622  
                 100 
               
               
                 12.8 ± 0.1 
                 6.938 ± 0.055 
                 34 
               
               
                 14.7 ± 0.1 
                 6.034 ± 0.041 
                 53 
               
               
                 17.5 ± 0.1 
                 5.076 ± 0.029 
                 34 
               
               
                 20.2 ± 0.1 
                 4.396 ± 0.022 
                 54 
               
               
                 21.8 ± 0.1 
                 4.079 ± 0.019 
                 31 
               
               
                 24.7 ± 0.1 
                 3.609 ± 0.014 
                 33 
               
               
                 25.9 ± 0.1 
                 3.436 ± 0.013 
                 32 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 7 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 63   k.    
     In an embodiment, Form 7 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 113 . 
     In an embodiment, there is provided crystalline Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate. 
     Form 8 may be characterised as having an XRPD pattern with a peak at 4.9 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 9.2, 12.4, 13.8 and 14.9 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 18.2 and 21.5 °2θ±0.2°θ. 
     In an embodiment, Form 8 has an XRPD pattern with peaks at the positions listed in Table 122 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 122 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                 4.9 ± 0.1 
                 18.035 ± 0.375 
                 68 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 8 has an XRPD pattern with peaks at the positions listed in Table 123 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 123 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.9 ± 0.1 
                 18.035 ± 0.375  
                 68 
               
               
                  9.2 ± 0.1 
                 9.592 ± 0.105 
                 57 
               
               
                 12.4 ± 0.1 
                 7.156 ± 0.058 
                 76 
               
               
                 13.8 ± 0.1 
                 6.440 ± 0.047 
                 100 
               
               
                 14.9 ± 0.1 
                 5.950 ± 0.040 
                 77 
               
               
                 18.2 ± 0.1 
                 4.869 ± 0.027 
                 70 
               
               
                 21.5 ± 0.1 
                 4.129 ± 0.019 
                 94 
               
               
                   
               
            
           
         
       
     
     In yet another embodiment, Form 8 has an XRPD pattern with peaks at the positions listed in Table 124 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 124 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.9 ± 0.1 
                 18.035 ± 0.375  
                 68 
               
               
                  9.2 ± 0.1 
                 9.592 ± 0.105 
                 57 
               
               
                 12.4 ± 0.1 
                 7.156 ± 0.058 
                 76 
               
               
                 13.8 ± 0.1 
                 6.440 ± 0.047 
                 100 
               
               
                 14.9 ± 0.1 
                 5.950 ± 0.040 
                 77 
               
               
                 18.2 ± 0.1 
                 4.869 ± 0.027 
                 70 
               
               
                 20.6 ± 0.1 
                 4.314 ± 0.021 
                 56 
               
               
                 21.5 ± 0.1 
                 4.129 ± 0.019 
                 94 
               
               
                   
               
            
           
         
       
     
     In an embodiment, Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 631 . 
     In an embodiment, Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 114 . 
     According to another aspect of the present invention, there is provided the hydrosulfate salt of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate. 
     In an embodiment, the (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate is in crystalline form. The crystalline forms of the hydrosulfate salt were found in the experiments on the sulfate salt. The sulfate salt designated the number “crystalline 2 minus peaks” ( FIG. 63   e ) was found to be the hydrosulfate salt, not the sulfate salt. This crystalline Form of the hydrosulfate form is hereinafter designated “crystalline Form A” of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate. The sulfate salt designated the number “crystalline 5” ( FIG. 63   i ) was found to be the hydrosulfate salt, not the sulfate salt. This crystalline Form of the hydrosulfate form is hereinafter designated “crystalline Form B” of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate. 
     In an embodiment, Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate has an XRPD pattern with a peak at a °2θ value between 29.8 and 30.5 and a peak at a °2θ value between 32.0 and 32.8. The XRPD of Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate may have a further peak at a °2θ value between 13.5 and 14.2. The XRPD of Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate may have a still further peak at a °2θ value between 21.2 and 21.8, a still further peak at a ° 20 value between 21.9 and 22.5 and a still further peak at a °2θ value between 23.6 and 24.3. The XRPD of Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate may have a yet further peak at a °2θ value between 12.2 and 12.8 and a yet further peak at a °2θ value between 15.5 and 16.1. In one embodiment, crystalline Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate is characterised as having an XRPD pattern as shown in  FIG. 63   e.    
     In an embodiment, there is provided crystalline Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate 
     Form B may be characterised as having an XRPD pattern with peaks at 4.6, 9.2 and 12.6 °2θ±0.2 °2θ. The XRPD pattern may have further peaks at 16.0 and 18.2 °2θ±0.2 °2θ. The XRPD pattern may have still further peaks at 13.4, 14.0 and 14.9 °2θ±0.2°θ. 
     In an embodiment, Form B has an XRPD pattern with peaks at the positions listed in Table 125 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 125 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                  4.6 ± 0.1 
                 19.336 ± 0.432  
                 23 
               
               
                  9.2 ± 0.1 
                 9.623 ± 0.106 
                 57 
               
               
                 12.6 ± 0.1 
                 7.020 ± 0.056 
                 46 
               
               
                 16.0 ± 0.1 
                 5.529 ± 0.034 
                 66 
               
               
                 18.2 ± 0.1 
                 4.869 ± 0.027 
                 67 
               
               
                   
               
            
           
         
       
     
     In another embodiment, Form 5 has an XRPD pattern with peaks at the positions listed in Table 126 below. 
     
       
         
           
               
               
               
             
               
                 TABLE 126 
               
               
                   
               
               
                 °2θ 
                 d space (Å) 
                 Intensity % (I/Io) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  4.6 ± 0.1 
                 19.336 ± 0.432  
                 23 
               
               
                  8.3 ± 0.1 
                 10.705 ± 0.131  
                 15 
               
               
                  9.2 ± 0.1 
                 9.623 ± 0.106 
                 57 
               
               
                 10.8 ± 0.1 
                 8.230 ± 0.077 
                 18 
               
               
                 11.5 ± 0.1 
                 7.715 ± 0.068 
                 19 
               
               
                 12.6 ± 0.1 
                 7.020 ± 0.056 
                 46 
               
               
                 12.7 ± 0.1 
                 6.954 ± 0.055 
                 23 
               
               
                 13.4 ± 0.1 
                 6.613 ± 0.050 
                 20 
               
               
                 14.0 ± 0.1 
                 6.330 ± 0.045 
                 22 
               
               
                 14.9 ± 0.1 
                 5.962 ± 0.040 
                 25 
               
               
                 15.6 ± 0.1 
                 5.688 ± 0.037 
                 30 
               
               
                 16.0 ± 0.1 
                 5.529 ± 0.034 
                 66 
               
               
                 16.8 ± 0.1 
                 5.274 ± 0.031 
                 44 
               
               
                 18.0 ± 0.1 
                 4.934 ± 0.027 
                 37 
               
               
                 18.2 ± 0.1 
                 4.869 ± 0.027 
                 67 
               
               
                 18.7 ± 0.1 
                 4.745 ± 0.025 
                 17 
               
               
                 19.7 ± 0.1 
                 4.502 ± 0.023 
                 38 
               
               
                 20.0 ± 0.1 
                 4.435 ± 0.022 
                 24 
               
               
                 21.1 ± 0.1 
                 4.211 ± 0.020 
                 28 
               
               
                 21.6 ± 0.1 
                 4.124 ± 0.019 
                 49 
               
               
                 21.8 ± 0.1 
                 4.073 ± 0.019 
                 39 
               
               
                 22.2 ± 0.1 
                 4.003 ± 0.018 
                 29 
               
               
                 23.7 ± 0.1 
                 3.748 ± 0.016 
                 30 
               
               
                 24.4 ± 0.1 
                 3.653 ± 0.015 
                 36 
               
               
                 24.7 ± 0.1 
                 3.600 ± 0.014 
                 77 
               
               
                 25.2 ± 0.1 
                 3.533 ± 0.014 
                 45 
               
               
                 26.6 ± 0.1 
                 3.356 ± 0.012 
                 100 
               
               
                 27.5 ± 0.1 
                 3.245 ± 0.012 
                 24 
               
               
                   
               
            
           
         
       
     
     In another embodiment, crystalline Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate is characterised as having an XRPD pattern as shown in  FIG. 63   i.    
     In an embodiment, Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate is characterised as having an XRPD pattern as shown in  FIG. 115 . 
     According to another aspect of the present invention, there is provided compound 2 in amorphous form, i.e. (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione in amorphous form. In an embodiment, the amorphous form of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione is characterised as having an XRPD pattern as shown in  FIG. 70 . 
     According to another aspect of the present invention, there is provided processes for preparing the salts and polymorphs described above. Each of the processes detailed in the Experimental represent alternative embodiments of the processes of the present invention. 
     According to another aspect of the present invention, there is provided a pharmaceutical composition comprising a salt or polymorph as described above together with one or more pharmaceutical excipients. The pharmaceutical compositions may be as described in WO2004/033447. 
     In this specification, crystalline and low crystalline forms of the same polymorph are described. For example, the adipate salt exists in crystalline Form 1, as well as low crystalline Form 1. Forms having the same number but specified as being either crystalline or low crystalline refer to the same polymorph. Reasons for XRPD patterns showing the form as a low crystalline form are well known to those skilled in the art. 
     In this specification, the term “compound 2” refers to (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione free base. 
    
    
     
       Reference is made to the accompanying Figures, which show: 
         FIG. 1   a  XRPD pattern of L-tartrate 
         FIG. 1   b  XRPD pattern of Malonate 
         FIG. 1   c  XRPD pattern of Tosylate, Form A 
         FIG. 1   d  XRPD pattern of (1R)-10-Camphorsulfonate 
         FIG. 1   e  XRPD pattern of Fumarate 
         FIG. 2  DSC and TG data for malonate salt 
         FIG. 3   a  XRPD pattern of L-tartrate salt: Form A 
         FIG. 3   b  XRPD pattern of L-tartrate salt: Form B 
         FIG. 4  Proton NMR of tartrate salt, Form A 
         FIG. 5  Proton NMR of tartrate salt, Form B 
         FIG. 6   a  XRPD pattern of tosylate salt: Form A (same as  FIG. 1   c ) 
         FIG. 6   b  XRPD pattern of tosylate salt: Form B 
         FIG. 6   c  XRPD pattern of tosylate salt: Form C 
         FIG. 6   d  XRPD pattern of tosylate salt: Form D 
         FIG. 6   e  XRPD pattern of tosylate salt: Form E 
         FIG. 6   f  XRPD pattern of tosylate salt: Form F (also called crystal modification X) 
         FIG. 6   g  XRPD pattern of tosylate salt: Form G 
         FIG. 6   h  XRPD pattern of tosylate salt: Form H (also called crystal modification Y) 
         FIG. 7  Proton NMR of tosylate salt, Form A 
         FIG. 8  DSC and TG data for the tosylate salt, Form A 
         FIG. 9  Proton NMR of tosylate salt, Form B 
         FIG. 10  DSC and TG data for tosylate salt, Form B 
         FIG. 11  Proton NMR of tosylate salt, Form C 
         FIG. 12  DSC and TG data for tosylate salt, Form C 
         FIG. 13  Proton NMR of tosylate salt, Form D 
         FIG. 14  Proton NMR of tosylate salt, Form E 
         FIG. 15  DSC and TG data for tosylate salt, Form E 
         FIG. 16  Proton NMR of tosylate salt, Form F (also called crystal modification X) 
         FIG. 17  DSC and TG data for tosylate salt, Form F 
         FIG. 18  Proton NMR of tosylate salt, Form G 
         FIG. 19  Proton NMR of tosylate salt, Form H (also called crystal modification Y) 
         FIG. 20  DSC and TG data for tosylate salt, Form H 
         FIG. 21   a  XRPD pattern of acetate salt: crystalline 1, scale-up 
         FIG. 21   b  XRPD pattern of acetate salt: crystalline 1, wellplate, well no. A3 
         FIG. 22  Proton NMR of acetate salt 
         FIG. 23  DSC and TG data for the acetate salt 
         FIG. 24   a  XRPD pattern of adipate salt: crystalline 1, scale-up 
         FIG. 24   b  XRPD pattern of adipate salt: crystalline 1, well plate, well no. B2 
         FIG. 24   c  XRPD pattern of adipate salt: low crystalline 1, well plate, well no. B1 
         FIG. 24   d  XRPD pattern of adipate salt: crystalline 1-peaks, well plate, well no. B6 
         FIG. 25  Proton NMR of adipate salt 
         FIG. 26  DSC and TG data for the adipate salt 
         FIG. 27   a  XRPD pattern of citrate salt: crystalline 1, scale-up 
         FIG. 27   b  XRPD pattern of citrate salt: crystalline 2, scale-up 
         FIG. 27   c  XRPD pattern of citrate salt: crystalline 1, well plate, well no. C3 
         FIG. 27   d  XRPD pattern of citrate salt: low crystalline 1, well plate, well no. C4 
         FIG. 28  Proton NMR of citrate salt, crystalline 1 
         FIG. 29  Proton NMR of citrate salt, crystalline 2 
         FIG. 30  Proton NMR of citrate salt, crystalline 2 
         FIG. 31  DSC and TG data for the citrate salt, crystalline 2 
         FIG. 32   a  XRPD pattern of gentisate salt: crystalline 1, scale-up 
         FIG. 32   b  XRPD pattern of gentisate salt: crystalline 1, well plate, well no. D5 
         FIG. 32   c  XRPD pattern of gentisate salt: crystalline 2, well plate, well no. D6 
         FIG. 33  Proton NMR of gentisate salt, crystalline 1 
         FIG. 34  Proton NMR of gentisate salt, crystalline 2 
         FIG. 35   a  XRPD pattern of glutarate salt: crystalline 1, scale-up 
         FIG. 35   b  XRPD pattern of glutarate salt: crystalline 1, well plate, well no. E1 
         FIG. 35   c  XRPD pattern of glutarate salt: low crystalline 1, well plate, well no. E3 
         FIG. 36  Proton NMR of glutarate salt 
         FIG. 37   a  XRPD pattern of glycolate salt: crystalline 1, scale-up 
         FIG. 37   b  XRPD pattern of glycolate salt: crystalline 1, well plate, well no. F1 
         FIG. 37   c  XRPD pattern of glycolate salt: low crystalline 1, well plate, well no. F2 
         FIG. 38  Proton NMR of glycolate salt 
         FIG. 39  DSC and TG data for the glycolate salt 
         FIG. 40   a  XRPD pattern of hydrobromide salt: crystalline 1, scale-up 
         FIG. 40   b  XRPD pattern of hydrobromide salt: crystalline 3, scale-up 
         FIG. 40   c  XRPD pattern of hydrobromide salt: crystalline 1, well plate, well no. All 
         FIG. 40   d  XRPD pattern of hydrobromide salt: crystalline 2, well plate, well no. A9 
         FIG. 40   e  XRPD pattern of hydrobromide salt: low crystalline 2, well plate, well no. A2 
         FIG. 41  Proton NMR of hydrobromide salt, crystalline 1 
         FIG. 42  Proton NMR of hydrobromide salt, crystalline 2 
         FIG. 43  Proton NMR of hydrobromide salt, crystalline 3 
         FIG. 44  DSC and TG data for the hydrobromide salt, crystalline 1 
         FIG. 45  XRPD pattern of lactate salt: crystalline 1, well plate, well no. B12 
         FIG. 46  Proton NMR of lactate salt 
         FIG. 47   a  XRPD pattern of L-malate salt: crystalline 1, scale-up 
         FIG. 47   b  XRPD pattern of L-malate salt: crystalline 1, well plate, well no. G6 
         FIG. 48  Proton NMR of L-malate salt 
         FIG. 49   a  XRPD pattern of maleate salt: crystalline 1+peaks, scale-up 
         FIG. 49   b  XRPD pattern of maleate salt: crystalline 1, well plate, well no. C5 
         FIG. 49   c  XRPD pattern of maleate salt: crystalline 1+one peak, well plate, well no. C11 
         FIG. 49   d  XRPD pattern of maleate salt: low crystalline 1, well plate, well no. C11 
         FIG. 50  Proton NMR of maleate salt 
         FIG. 51   a  XRPD pattern of phosphate salt: crystalline 1, well plate, well no. G11 
         FIG. 51   b  XRPD pattern of phosphate salt: crystalline 1+peaks, well plate, well no. G6 
         FIG. 51   c  XRPD pattern of phosphate salt: low crystalline 1, well plate, well no. G5 
         FIG. 51   d  XRPD pattern of phosphate salt: crystalline 2, wellplate, well no. G1 
         FIG. 51   e  XRPD pattern of phosphate salt: crystalline 3, wellplate, well no. G7 
         FIG. 51   f  XRPD pattern of phosphate salt: crystalline 4, wellplate, well no. G8 
         FIG. 51   g  XRPD pattern of phosphate salt: crystalline 5 (also called crystal modification X), scale-up 
         FIG. 51   h  XRPD pattern of phosphate salt: crystalline 6, scale-up 
         FIG. 51   i  XRPD pattern of phosphate salt: low crystalline 7, scale-up 
         FIG. 52  XRPD pattern of phosphate salt: crystalline 8, scale-up 
         FIG. 53  Proton NMR of phosphate salt, crystalline 2 
         FIG. 54  Proton NMR of phosphate salt, crystalline 3 
         FIG. 55  Proton NMR of phosphate salt; crystalline 4 
         FIG. 56  Proton NMR of phosphate salt, crystalline 5 (also called crystal modification X) 
         FIG. 57  Proton NMR data for the phosphate salt, crystalline 8 
         FIG. 58  DSC and TG data for the phosphate salt, crystalline 8 
         FIG. 59  XRPD patterns of succinate salt (top to bottom) 
         FIG. 60  Proton NMR of succinate salt, crystalline 1 
         FIG. 61  Proton NMR of succinate salt, crystalline 2 
         FIG. 62  Proton NMR of succinate salt, crystalline 3 
         FIG. 63   a  XRPD pattern of sulfate salt: crystalline 1, well plate, well no. F2 
         FIG. 63   b  XRPD pattern of sulfate salt: low crystalline 1, well plate 95730, well no. F4 
         FIG. 63   d  XRPD pattern of sulfate salt: crystal modification X (also referred to as crystalline 2), well plate 95730, well no. F6 
         FIG. 63   e  XRPD pattern of hydrosulfate salt: Form A (also referred to as crystalline 2 minus peaks), well plate 96343, well no. F6 
         FIG. 63   f  XRPD pattern of sulfate salt: crystalline 3, well plate, well no. F1 
         FIG. 63   g  XRPD pattern of sulfate salt: crystal modification Y (also referred to as crystalline 4), well plate, well no. F5 
         FIG. 63   h  XRPD pattern of sulfate salt: crystalline 1, scale-up 
         FIG. 63   i  XRPD pattern of hydrosulfate salt: Form B (also referred to as crystalline 5), scale-up 
         FIG. 63   j  XRPD pattern of sulfate salt: crystalline 6, scale-up 
         FIG. 63   k  XRPD pattern of sulfate salt: crystalline 7, scale-up 
         FIG. 631  XRPD pattern of sulfate salt: low crystalline 8, scale-up 
         FIG. 64  Proton NMR of sulfate salt, crystalline 1 
         FIG. 65  DSC and TG data for sulfate salt, crystalline 1 
         FIG. 66  Proton NMR of hydrosulfate salt, Form A (also referred to as crystalline 2 minus peaks) 
         FIG. 67  Proton NMR of hydrosulfate salt, Form B (also referred to as crystalline 5) 
         FIG. 68  Proton NMR of sulfate salt, crystalline 6 
         FIG. 69  Proton NMR of sulfate salt, crystalline 7 
         FIG. 70  XRPD pattern of amorphous form of compound 2 
         FIG. 71  XRPD pattern of Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate. 
         FIG. 72  XRPD pattern of Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione L-tartrate 
         FIG. 73  XRPD pattern of Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malonate 
         FIG. 74  XRPD pattern of Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione camsylate 
         FIG. 75  XRPD pattern of Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione fumarate  FIG. 76  XRPD pattern of Form A of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate 
         FIG. 77  XRPD pattern of Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate 
         FIG. 78  XRPD pattern of Form C of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate 
         FIG. 79  XRPD pattern of Form E of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate 
         FIG. 80  XRPD pattern of crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate 
         FIG. 81  XRPD pattern of Form G of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate 
         FIG. 82  XRPD pattern of crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione tosylate 
         FIG. 83  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione acetate 
         FIG. 84  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione adipate  FIG. 85  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glutarate  FIG. 86  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate 
         FIG. 87  XRPD pattern of Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate 
         FIG. 88  XRPD pattern of Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione succinate 
         FIG. 89  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide 
         FIG. 90  XRPD pattern of Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide 
         FIG. 91  XRPD pattern of Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrobromide 
         FIG. 92  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate 
         FIG. 93  XRPD pattern of Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione maleate 
         FIG. 94  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate 
         FIG. 95  XRPD pattern of Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate 
         FIG. 96  XRPD pattern of Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate 
         FIG. 97  XRPD pattern of Form 4 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate 
         FIG. 98  XRPD pattern of crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate 
         FIG. 99 . XRPD pattern of Form 6 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate 
         FIG. 100  XRPD pattern of Form 7 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate 
         FIG. 101  XRPD pattern of Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione phosphate 
         FIG. 102  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate 
         FIG. 103  XRPD pattern of Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione gentisate 
         FIG. 104  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate 
         FIG. 105  XRPD pattern of Form 2 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione citrate 
         FIG. 106  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione malate 
         FIG. 107  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione glycolate 
         FIG. 108  XRPD pattern of Form 1 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate 
         FIG. 109  XRPD pattern of crystal modification X of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate 
         FIG. 110  XRPD pattern of Form 3 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate 
         FIG. 111  XRPD pattern of crystal modification Y of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate 
         FIG. 112  XRPD pattern of Form 6 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate 
         FIG. 113  XRPD pattern of Form 7 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate 
         FIG. 114  XRPD pattern of Form 8 of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione sulfate 
         FIG. 115  XRPD pattern of Form B of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrosulfate 
         FIG. 116  XRPD pattern of compound 2 
     
    
    
     EXPERIMENTAL DETAILS 
     A salt and polymorph screen was undertaken which involved various crystallisation techniques, as explained below. 
     1. Solvent-Based Crystallization Techniques 
     a. Fast Evaporation (FE) 
     Solutions of compound 2 were prepared in various solvents in which samples were vortexed or sonicated between aliquot additions. Once a mixture reached complete dissolution, as judged by visual observation, the solution was filtered through a 0.2-μm nylon filter. The filtered solution was allowed to evaporate at ambient conditions in an open vial. The solids were isolated and analyzed. 
     b. Slow Evaporation (SE) 
     Solutions of compound 2 were prepared in various solvents in which samples were vortexed or sonicated between aliquot additions. Once a mixture reached complete dissolution, as judged by visual observation, the solution was filtered through a 0.2-μm nylon filter. The filtered solution was allowed to evaporate at ambient conditions in a vial covered with a loose cap or perforated aluminum foil. The solids were isolated and analyzed. 
     c. Slurry Experiments 
     Solutions of compound 2 were prepared by adding enough solids to a given solvent at ambient conditions so that undissolved solids were present. The mixture was then loaded on a rotary wheel or an orbit shaker in a sealed vial at either ambient or elevated temperature for a certain period of time, typically 7 days. The solids were isolated by vacuum filtration or by drawing off or decanting the liquid phase and allowing the solids to air dry at ambient conditions prior to analysis. 
     d. Crash Precipiation 
     Solutions of compound 2 were prepared in various solvents in which samples were agitated or sonicated to facilitate dissolution. The resulting solutions (sometimes filtered) were transferred into vials containing a known volume of antisolvent and/or aliquots of antisolvent were added to the solutions until precipitation persisted. If precipitation was insufficient, some samples were left at ambient temperature. The solids were isolated by decanting the liquid phase and allowing the solids to air dry at ambient conditions prior to analysis. 
     e. Slow Cool 
     Solutions of compound 2 were prepared in various solvents in which samples were heated with agitation to facilitate dissolution. The solutions were cooled by shutting off the heat source. If precipitation was insufficient, samples were refrigerated or evaporated. The solids were isolated by vacuum filtration. 
     2. Well Plate Crystallization Techniques 
     a. Wellplate Salt Preparations 
     Preparation of salts was carried out in 96-well polypropylene plates using the following general procedure. API solutions were prepared by dissolving compound 2 free base in acetone, methanol, methyl ethyl ketone, tetrahydrofuran or 2,2,2-trifluoroethanol at approximately 10 mg/mL, adding 0.1 mL of these solutions per well. Dilute acid solutions were added (methanol solutions, generally 0.1M) to the wells at slightly more than one molar equivalent with respect to the API. Each API/acid combination was prepared in triplicate and wells with only the API solutions: were also prepared for comparison. The plates were covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 or 11 days. Some evaporation occurred during mixing. The plates were observed after 3 days by optical microscopy and returned to the shaker. Upon removal from the shaker, they were observed visually for color under standard laboratory lighting. The plates were left uncovered to complete evaporation under ambient conditions for final microscopic evaluation and XRPD analysis. 
     b. General Salt Preparation procedure 
     To a glass vial of compound 2 dissolved in various solvents, slightly more than one molar equivalent of various counterion solutions were added. Samples were allowed to slurry and/or evaporate at ambient temperature in a laboratory fume hood. Often, antisolvent was added to precipitate solids. The resulting solids were isolated by filtration or solvent decantation (often preceded by centrifugation), examined by polarized light microscopy and generally submitted for XRPD analysis. 
     c. Fast Evaporation 
     A well plate containing various solutions was allowed to stand, uncovered, at ambient conditions to allow the solutions to evaporate. The solids were analyzed in the well plate. 
     d. Recrystallization Techniques 
     Solutions were prepared by dispensing 75 μL of methanol into each well of a well plate containing solids from previous experiments. The well plate was then covered and attached to an orbit shaker for 30 minutes to 1 hour. An equal volume (75 μL) of various antisolvents was added to each well, and the solutions were allowed to fast evaporate at ambient conditions. The solids were analyzed in the well plate. 
     Instrumental Techniques 
     The characterisation of the polymorphs involved various analytical techniques, as explained below. 
     A. X-Ray Powder Diffraction (XRPD) 
     Shimadzu XRD-6000 Diffractometer 
     Analyses were carried out on a Shimadzu XRD-6000 X-ray powder diffractometer using Cu Kα radiation. The instrument is equipped with a long fine focus X-ray tube. The tube voltage and amperage were set at 40 kV and 40 mA, respectively. The divergence and scattering slits were set at 1° and the receiving slit was set at 0.15 mm. Diffracted radiation was detected by a NaI scintillation detector. A theta-two theta continuous scan at 3°/min (0.4 sec/0.02° step) from 2.5 to 40 °2θ was used. A silicon standard was analyzed each day to check the instrument alignment. Samples were analyzed in an aluminum sample holder with a silicon well. 
     Inel XRG-3000 Diffractometer 
     X-ray powder diffraction (XRPD) analyses were performed using an Inel XRG-3000 diffractometer equipped with a CPS (Curved Position Sensitive) detector with a 20 range of 120°. Real time data were collected using Cu-Kα radiation starting at approximately 4 °2θ at a resolution of 0.03 °2θ. The tube voltage and amperage were set to 40 kV and 30 mA, respectively. The monochromator slit was set at 5 mm by 160 μm. The pattern is displayed from 2.5-40 °2. Samples were prepared for analysis by packing them into thin-walled glass capillaries. Each capillary was mounted onto a goniometer head that is motorized to permit spinning of the capillary during data acquisition. The samples were analyzed for 5 or 10 min. Instrument calibration was performed using a silicon reference standard. 
     Bruker D-8 Discover Diffractometer 
     XRPD patterns were collected with a Bruker D-8 Discover diffractometer and Bruker&#39;s General Area Diffraction Detection System (GADDS, v. 4.1.20). An incident beam of Cu Kα radiation was produced using a fine-focus tube (40 kV, 40 mA), a Göbel mirror, and a 0.5 mm double-pinhole collimator. The samples were positioned for analysis by securing the well plate to a translation stage and moving each sample to intersect the incident beam. The samples were analyzed using a transmission geometry. The incident beam was scanned and rastered over the sample during the analysis to optimize orientation statistics. A beam-stop was used to minimize air scatter from the incident beam at low angles. Diffraction patterns were collected using a Hi-Star area detector located 15 cm from the sample and processed using GADDS. The intensity in the GADDS image of the diffraction pattern was integrated using a step size of 0.04 °2θ. The integrated patterns display diffraction intensity as a function of 2θ. Prior to the analysis a silicon standard was analyzed to verify the Si 111 peak position. The instrument was operated under non-cGMP conditions, and the results are non-cGMP. 
     PatternMatch 2.4.0 software, combined with visual inspection, was used to identify peak positions for each form. “Peak position” means the maximum intensity of a peaked intensity profile. Where data collected on the INEL diffractometer was used, it was first background-corrected using PatternMatch 2.4.0. 
     PatternMatch 2.4.0 was used for all peak identification. Peak positions were reproducible to within 0.1 °2θ. Therefore, all peak positions reported in tables used this precision as indicated by the number following the ± in the 2θ column. All peak positions have been converted to (wavelength-independent) d space using a wavelength of 1.541874 Å and the precision at each position is indicated as well (note that the precision is not constant in d space). It will be noted that the precision of within 0.1 °2θ was used to determine reproducability of peak positions. It will be appreciated that peak positions may vary to a small extent depending on which apparatus is used to analyse a sample. Therefore, all definitions of the polymorphs which refer to peak positions at °2θ values are understood to be subject to variation of ±0.2 °2θ. Unless otherwise stated (for example in the Tables with ±values), the °2θ values of the peak positions are ±0.2 °2θ. 
     B. Differential Scanning Calorimetry (DSC) 
     Differential scanning calorimetry (DSC) was performed using a TA Instruments differential scanning calorimeter 2920 and Q1000. The sample was placed into an aluminum DSC pan, and the weight accurately recorded. The pan was covered with a lid and then crimped or non-crimped pan configuration was used. The sample cell was equilibrated at 25° C. and heated under a nitrogen purge at a rate of 10° C./min, up to a final temperature of 250, or 300° C. Indium metal was used as the calibration standard. Reported temperatures are at the transition maxima. 
     C. Thermogravimetry (TG) 
     Thermogravimetric (TG) analyses were performed using a TA Instruments 2950 thermogravimetric analyzer. Each sample was placed in an aluminum sample pan and inserted into the TG furnace. The furnace was either equilibrated at 25° C. or directly heated under nitrogen at a rate of 10° C./min, up to a final temperature of 350° C. Nickel and Alumel™ were used as the calibration standards. 
     D. NMR Spectroscopy 
     Solution 1D  1 H NMR Spectroscopy 
     Solution  1 H NMR spectra were acquired at ambient temperature with a Varian  UNITY INOVA-400 spectrometer at a  1 H Larmor frequency of 399.795 MHz. The sample was dissolved in MeOH-d 4 . The spectrum was acquired with a  1 H pulse width of 8.2, 8.4, 8.5 or 10 μs, a 2.50 second acquisition time, a 5 second delay between scans, a spectral width of 6400 Hz with 32000 data points, and 40 co-added scans. The free induction decay (FID) was processed using Varian VNMR 6.1C software with 32000 points. The residual peak from incompletely deuterated methanol is at approximately 3.3 ppm. The relatively broad peak at approximately 4.88 ppm is due to water. The spectrum was referenced to internal tetramethylsilane (TMS) at 0.0 ppm. 
     Solution 1D  1 H NMR Spectroscopy (SDS, Inc.) 
     The solution  1 H NMR spectrum was acquired by Spectral Data Services of Champaign, Ill. at 25° C. with a Varian  UNITY INOVA-400 spectrometer at a  1 H Larmor frequency of 399.798 MHz. The sample was dissolved in methanol-d 4 . The spectrum was acquired with a  1 H pulse width of 7.0 μs, a 5 second delay between scans, a spectral width of 7000 Hz with 35K data points, and 40 co-added scans. The free induction decay (FID) was processed with 64K points and an exponential line broadening factor of 0.2 Hz to improve the signal-to-noise ratio. The residual peak from incompletely deuterated methanol is at approximately 3.3 ppm. 
     Results—Solvent-Based Crystallization Screen 
     Camsylate Salt 
     The initial lot of the camsylate salt was prepared as follows. 
     To a suspension of compound 2 (0.93 g, 3 mmol) in MeOH (20 ml) was added a solution of (1R)-(−)-camphorsulfonic acid (0.70 g, 3 mmol) in MeOH (5 ml) at 50° C. with stirring. The mixture was heated to reflux, allowed to cool naturally to 20-25° C. with stirring, aged at 20-25° C. for 2 h. The precipitate was collected, washed with MeOH (10 ml), dried in vacuum at 45° C. to a constant weight. Yield 1.39 g (85%). 
     A polymorph screen was carried out on the (1R)-10-camphorsulfonate salt (camsylate salt) of compound 2 using slurry and slow evaporation experiments (Table 1A). The XRPD pattern of the camsylate salt is shown in  FIG. 1   d . No other forms were found in the screen. 
     
       
         
           
               
             
               
                 TABLE 1A 
               
             
            
               
                   
               
               
                 Polymorph Screen of (1R)-10-Camphorsulfonate salt 
               
            
           
           
               
               
               
               
            
               
                   
                 Solvent 
                 Conditions a   
                 XRPD Result 
               
               
                   
                   
               
               
                   
                 acetone 
                 slurry 
                 camsylate 
               
               
                   
                 acetonitrile 
                 slurry 
                 camsylate 
               
               
                   
                 1,4-dioxane 
                 slurry 
                 camsylate 
               
               
                   
                 ethanol 
                 slurry 
                 camsylate 
               
               
                   
                 ethyl acetate 
                 slurry 
                 camsylate 
               
               
                   
                 iso-propanol 
                 slurry 
                 camsylate 
               
               
                   
                 methanol 
                 SE 
                 camsylate 
               
               
                   
                 methyl ethyl ketone 
                 slurry 
                 camsylate 
               
               
                   
                 tetrahydrofuran (THF) 
                 slurry 
                 camsylate 
               
               
                   
                 toluene 
                 slurry 
                 camsylate 
               
               
                   
                 2,2,2-trifluoroethanol 
                 SE 
                 camsylate 
               
               
                   
                 water 
                 slurry 
                 camsylate 
               
               
                   
                   
               
               
                   
                   a SE = slow evaporation 
               
            
           
         
       
     
     Fumarate Salt 
     The initial lot of the fumarate salt was prepared as follows. 
     Compound 2 (0.93 g, 3 mmol) was dissolved in a mixture of MeOH (20 ml) and DCM (5 ml) with heating to 40-45° C. and stirring. To the resulting clear solution fumaric acid (0.35 g, 3 mmol) in MeOH (10 ml) was added, the mixture was allowed to cool naturally to 20-25° C. with stirring (crystallisation occurred). The mixture was aged in ice for 1 h, the precipitate was collected, washed with MeOH (5 ml), dried in vacuum at 45° C. to a constant weight. Yield 0.82 g (74%). 
     A polymorph screen was carried out on the fumarate salt of compound 2 using slurry and fast evaporation experiments (Table 2A). The XRPD pattern of the fumarate salt is shown in  FIG. 1   e . No other forms were found in the screen. 
     
       
         
           
               
             
               
                 TABLE 2A 
               
             
            
               
                   
               
               
                 Fumarate salt 
               
            
           
           
               
               
               
               
            
               
                 Solvent 
                 Conditions a   
                 Habit/Description 
                 XRPD Result b   
               
               
                   
               
               
                 acetone 
                 slurry, 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 yellow plates and needles, 
                 fumarate 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 acetonitrile 
                 slurry, 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear glassy film, not 
                 — 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 1,4-dioxane 
                 slurry, 
                 white plates, birefringent 
                 fumarate 
               
               
                   
                 7 days 
               
               
                   
                 FE (liquid phase 
                 clear glassy film, not 
                 — 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 ethanol 
                 slurry, 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 light yellow needles and 
                 — 
               
               
                   
                 from slurry) 
                 blades, birefringent 
               
               
                 ethyl acetate 
                 slurry, 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear, morphology unknown, 
                 — 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 iso-propanol 
                 slurry, 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear needles, birefringent; 
                 — 
               
               
                   
                 from slurry) 
                 clear glassy film, not 
               
               
                   
                   
                 birefringent 
               
               
                 methanol 
                 slurry, 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 yellow plates and morphology 
                 fumarate 
               
               
                   
                 from slurry) 
                 unknown, birefringent 
               
               
                 methyl ethyl ketone 
                 slurry, 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear fibers and morphology 
                 — 
               
               
                   
                 from slurry) 
                 unknown, birefringent 
               
               
                 tetrahydrofuran 
                 slurry, 
                 white plates and morphology 
                 fumarate 
               
               
                 (THF) 
                 7 days 
                 unknown, birefringent 
               
               
                   
                 FE (liquid phase 
                 clear fibers, birefringent 
                 — 
               
               
                   
                 from slurry) 
               
               
                 toluene 
                 slurry, 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear fibers, birefringent 
                 — 
               
               
                   
                 from slurry) 
               
               
                 2,2,2- 
                 slurry, 
                 white, morphology unknown, 
                 fumarate, l.c. 
               
               
                 trifluoroethanol 
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 white, morphology unknown, 
                 fumarate 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 water 
                 FE 
                 white, dendridic formations, 
                 fumarate 
               
               
                   
                   
                 birefringent 
               
               
                   
               
               
                   a FE = fast evaporation 
               
               
                   b l.c. = low crystallinity 
               
            
           
         
       
     
     Malonate Salt 
     The initial lot of the malonate salt was prepared as follows. 
     To a suspension of compound 2 (0.93 g, 3 mmol) in MeOH (10 ml) was added a solution of malonic acid (0.31 g, 3 mmol) in MeOH (5 ml) at 50° C. with stirring. The mixture was heated to reflux to obtain a clear solution, allowed to cool naturally to 20-25° C. with stirring (crystallisation occurred), aged in ice for 30 min. The precipitate was collected, washed with MeOH (3 ml), dried in vacuum at 45° C. to a constant weight. Yield 1.12 g (90%). 
     A polymorph screen of the malonate salt was carried out using slurry and fast evaporation crystallization techniques (Table 3A). The XRPD pattern of the initial lot of the malonate salt is shown in  FIG. 1   b . No new forms were found in the abbreviated polymorph screen. 
     
       
         
           
               
             
               
                 TABLE 3A 
               
             
            
               
                   
               
               
                 Polymorph Screen of Malonate Salt 
               
            
           
           
               
               
               
               
            
               
                 Solvent 
                 Conditions a   
                 Habit/Description 
                 XRPD Result 
               
               
                   
               
               
                 acetone 
                 slurry, 
                 clear solution 
                 — 
               
               
                   
                 7 days 
               
               
                   
                 FE 
                 yellow, morphology 
                 malonate 
               
               
                   
                   
                 unknown, partially 
               
               
                   
                   
                 birefringent 
               
               
                 acetonitrile 
                 slurry, 
                 white, morphology unknown, 
                 malonate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 white needles and blades, 
                 — 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 1,4-dioxane 
                 slurry, 
                 white, morphology unknown, 
                 malonate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear glassy film, not 
                 — 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 ethanol 
                 slurry, 
                 white, morphology unknown, 
                 malonate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 white, morphology unknown, 
                 malonate 
               
               
                   
                 from slurry) 
                 partially birefringent 
               
               
                 ethyl 
                 slurry, 
                 white, morphology unknown, 
                 malonate 
               
               
                 acetate 
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear oily film, not 
                 — 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 iso- 
                 slurry, 
                 white, morphology unknown, 
                 malonate 
               
               
                 propanol 
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 translucent glassy film, not 
                 — 
               
               
                   
                 from slurry) 
                 birefringent; white, 
               
               
                   
                   
                 morphology unknown, 
               
               
                   
                   
                 birefringent 
               
               
                 methanol 
                 FE 
                 white, morphology unknown, 
                 malonate 
               
               
                   
                   
                 birefringent 
               
               
                 methyl 
                 slurry, 
                 white, morphology unknown, 
                 malonate 
               
               
                 ethyl ketone 
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 yellow oily film, not 
                 — 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 tetrahydrofuran 
                 slurry, 
                 clear glassy film, not 
                 amorphous + peaks from 
               
               
                 (THF) 
                 7 days 
                 birefringent; clear plates, 
                 malonate 
               
               
                   
                   
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear fibers, birefringent 
                 — 
               
               
                   
                 from slurry) 
               
               
                 toluene 
                 slurry, 
                 white, morphology unknown, 
                 malonate 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 white fibers, birefringent 
                 — 
               
               
                   
                 from slurry) 
               
               
                 2,2,2- 
                 FE 
                 white fibers, birefringent 
                 malonate 
               
               
                 trifluoroethanol 
               
               
                 water 
                 FE 
                 white blades, birefringent 
                 malonate 
               
               
                   
               
               
                   a FE = fast evaporation 
               
            
           
         
       
     
     The malonate salt was characterized using thermal techniques (Table 4A,  FIG. 2 ). A weight loss of approximately 0.3% was observed in the range of 16 to 180° C. A sharp endotherm at approximately 201° C. in DSC accompanied by approx. 25% weight loss was probably due to simultaneous melt/decomposition. 
     
       
         
           
               
             
               
                 TABLE 4A 
               
             
            
               
                   
               
               
                 Characterization of Malonate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 A 
               
               
                   
                 DSC a   
                 endo 201 (266 J/g) 
               
               
                   
                 TGA b   
                  0.30 @ 16-180 
               
               
                   
                   
                 24.95 @ 180-215 
               
               
                   
                   
               
            
           
         
       
         
         
           
             a. endo=endotherm, temperatures (C°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
             b. weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
           
         
       
    
     L-Tartrate Salt 
     The initial lot of the L-tartrate salt was prepared as follows. 
     Compound 2 (0.93 g, 3 mmol) was dissolved in a mixture of MeOH (20 ml) and DCM (5 ml) with heating to 40-45° C. and stirring. To the resulting clear solution L-tartaric acid (0.45 g, 3 mmol) in MeOH (10 ml) was added, the solution was concentrated under reduced pressure to half of the initial volume and diluted with 2-propanol (20 ml) (crystallisation occurred). The suspension was cooled in ice to 0-5° C., aged for 30 min, the precipitate was collected, washed with 2-propanol (5 ml), dried in vacuum at 45° C. to a constant weight. Yield 1.08 g (78%). 
     A polymorph screen of the L-tartrate salt was carried out using slurry and fast evaporation crystallization techniques (Table 5A). The XRPD pattern of the initial lot of the L-tartrate salt exhibited an amorphous character ( FIG. 1   a ). 
     
       
         
           
               
             
               
                 TABLE 5A 
               
             
            
               
                   
               
               
                 Polymorph Screen L-Tartrate Salt 
               
            
           
           
               
               
               
               
            
               
                 Solvent 
                 Conditions a   
                 Habit/Description 
                 XRPD Result b   
               
               
                   
               
               
                 acetone 
                 FE 
                 white and yellow, 
                 amorphous 
               
               
                   
                   
                 morphology unknown, 
               
               
                   
                   
                 partially birefringent 
               
               
                 acetonitrile 
                 slurry, 
                 white, morphology unknown, 
                 low crystalline Form A 
               
               
                   
                 7 days 
                 partially birefringent 
               
               
                   
                 FE (filtrate from 
                 clear glassy film, not 
                 — 
               
               
                   
                 slurry) 
                 birefringent 
               
               
                   
                 slurry, 
                 white, morphology unknown, 
                 crystalline, possibly A + 
               
               
                   
                 7 days 
                 not birefringent 
                 peaks 
               
               
                   
                 (scale up) 
               
               
                 1,4-dioxane 
                 slurry, 
                 yellow glassy film, not 
                 amorphous 
               
               
                   
                 7 days 
                 birefringent 
               
               
                   
                 FE (liquid phase 
                 clear oily film, not 
                 — 
               
               
                   
                 from slurry) 
                 birefringent 
               
               
                 ethanol 
                 slurry, 
                 white, morphology unknown, 
                 IS 
               
               
                   
                 7 days 
                 not birefringent; clear glassy 
               
               
                   
                   
                 film, not birefringent 
               
               
                   
                 FE (liquid phase 
                 yellow, morphology 
                 amorphous + peaks 
               
               
                   
                 from slurry) 
                 unknown, birefringent 
               
               
                 ethyl acetate 
                 slurry, 
                 white, morphology unknown, 
                 Form B 
               
               
                   
                 7 days 
                 not birefringent 
               
               
                   
                 FE (filtrate from 
                 clear glassy film, not 
                 — 
               
               
                   
                 slurry) 
                 birefringent 
               
               
                   
                 slurry, 
                 white, morphology unknown, 
                 B minus peaks 
               
               
                   
                 7 days 
                 partially birefringent 
               
               
                   
                 (scale up) 
               
               
                 iso-propanol 
                 slurry, 
                 light yellow, morphology 
                 amorphous 
               
               
                   
                 7 days 
                 unknown, not birefringent 
               
               
                   
                 FE (filtrate from 
                 clear glassy film, not 
                 — 
               
               
                   
                 slurry) 
                 birefringent; white, 
               
               
                   
                   
                 morphology unknown, 
               
               
                   
                   
                 birefringent 
               
               
                 methanol 
                 FE 
                 white, morphology unknown, 
                 amorphous 
               
               
                   
                   
                 birefringent 
               
               
                 methyl ethyl 
                 slurry, 
                 light brown, morphology 
                 amorphous 
               
               
                 ketone 
                 7 days 
                 unknown, not birefringent 
               
               
                   
                 FE (filtrate from 
                 yellow oily film, not 
                 — 
               
               
                   
                 slurry) 
                 birefringent; clear 
               
               
                   
                   
                 morphology unknown, 
               
               
                   
                   
                 birefringent 
               
               
                 tetrahydrofuran 
                 slurry, 
                 white, morphology unknown, 
                 amorphous 
               
               
                 (THF) 
                 7 days 
                 not birefringent 
               
               
                   
                 FE (filtrate from 
                 clear fibers, birefringent 
                 — 
               
               
                   
                 slurry) 
               
               
                 toluene 
                 slurry, 
                 white, morphology unknown, 
                 amorphous 
               
               
                   
                 7 days 
                 not birefringent 
               
               
                   
                 liquid phase from 
                 clear glassy film, not 
                 — 
               
               
                   
                 slurry, FE 
                 birefringent 
               
               
                 2,2,2- 
                 slurry, 
                 clear solution with one white 
                 — 
               
               
                 trifluoroethanol 
                 3 days 
                 float 
               
               
                   
                 FE 
                 white, morphology unknown, 
                 amorphous 
               
               
                   
                   
                 not birefringent 
               
               
                 water 
                 FE 
                 yellow flakes, birefringent 
                 amorphous 
               
               
                   
               
               
                   a FE = fast evaporation 
               
               
                   b IS = insufficient sample 
               
            
           
         
       
     
     A low crystalline Form A and crystalline Form B resulted from slurry experiments in acetonitrile and ethyl acetate, respectively (Table 6A and Table 7A). The XRPD patterns of both forms are presented in  FIGS. 3   a  and  3   b . The proton NMR spectra for Forms A and B are shown in  FIG. 4  and  FIG. 5 , respectively. Based on NMR, low crystalline Form A contained residual amounts of acetonitrile, whereas crystalline Form B was likely an ethyl acetate mono-solvate. 
     
       
         
           
               
             
               
                 TABLE 6A 
               
             
            
               
                   
               
               
                 Characterization of L-Tartrate Salt, low crystalline Form A 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 low crystalline Form A 
               
               
                   
                   1 H NMR 
                 0.16 mole of CH 3 CN per 1 mole of 
               
               
                   
                   
                 compound 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7A 
               
             
            
               
                   
               
               
                 Characterization of L-Tartrate Salt, Form B 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline Form B 
               
               
                   
                   1 H NMR 
                 0.91 mole of EtOAc per 1 mole of 
               
               
                   
                   
                 compound 
               
               
                   
                   
               
            
           
         
       
     
     Tosylate Salt 
     The initial lot of the tosylate salt was prepared as follows. 
     To a suspension of compound (0.93 g, 3 mmol) in MeOH (10 ml) was added a solution of p-toluenesulfonic acid monohydrate (0.57 g, 3 mmol) in MeOH (5 ml) at 50° C. with stirring. The mixture was heated to reflux to obtain a clear solution, allowed to cool naturally to 20-25° C. with stirring (crystallisation occurred), aged in ice for 30 min. The precipitate was collected, washed with MeOH (3 ml), dried in vacuum at 45° C. to a constant weight. Yield 1.07 g (74%) 
     A polymorph screen of the tosylate salt was carried out using slurry and fast evaporation crystallization techniques (Table 8A). The initial lot of the tosylate salt was designated as Form A ( FIG. 1   c ). Seven new crystalline forms were obtained and designated alphabetically from B through H ( FIGS. 6   a  to  6   h ). The materials exhibiting new crystalline XRPD patterns were characterized by proton NMR and the NMR spectra were consistent with the compound structure, except for the spectrum of Form D. Forms B, C, E, F, and H were additionally characterized using thermal techniques. 
     
       
         
           
               
             
               
                 TABLE 8A 
               
             
            
               
                   
               
               
                 Polymorph Screen of Tosylate salt 
               
            
           
           
               
               
               
               
            
               
                 Solvent 
                 Conditions a   
                 Habit/Description 
                 XRPD Result 
               
               
                   
               
               
                 acetone 
                 FE 
                 clear, broken glass, 
                 amorphous 
               
               
                   
                   
                 birefringent 
               
               
                 acetonitrile 
                 slurry, 
                 white solid 
                 B 
               
               
                   
                 7 day 
               
               
                 1,4-dioxane 
                 FE, vac. oven 
                 clear glassy solid, not 
                 — 
               
               
                   
                   
                 birefringent 
               
               
                 ethanol 
                 FE 
                 white, dendridic formations, 
                 A + peaks 
               
               
                   
                   
                 birefringent 
               
               
                 ethyl acetate 
                 slurry, 
                 white solid 
                 F 
               
               
                   
                 7 days 
               
               
                   
                 slurry, 1 day 
                 — 
                 amorphous halo + 
               
               
                   
                   
                   
                 peaks 
               
               
                   
                 slurry, 4 days 
                 white solid 
                 F 
               
               
                   
                 slurry, 4 days 
                 white solid 
                 — 
               
               
                 iso-propanol 
                 slurry, 
                 white solid 
                 C 
               
               
                   
                 7 days 
               
               
                   
                 slurry, 1 day 
                 — 
                 amorphous + E 
               
               
                   
                   
                   
                 peaks 
               
               
                   
                 slurry, 4 days 
                 white solid 
                 C 
               
               
                   
                 slurry, 4 days 
                 white solid 
                 — 
               
               
                 methanol 
                 FE 
                 white solid, broken glass, not 
                 A + peaks 
               
               
                   
                   
                 birefringent and long needles, 
               
               
                   
                   
                 birefringent 
               
               
                 methyl ethyl 
                 FE 
                 dark red viscous liquid 
                 — 
               
               
                 ketone 
               
               
                 tetrahydrofuran 
                 slurry, 
                 white solid 
                 D 
               
               
                 (THF) 
                 7 days 
               
               
                   
                 slurry, 1 day 
                 — 
                 amorphous halo + 
               
               
                   
                   
                   
                 peaks 
               
               
                   
                 slurry, 4 days 
                 white solid 
                 H 
               
               
                   
                 slurry, 7 days 
                 white solid 
                 H 
               
               
                 toluene 
                 slurry, 
                 white solid 
                 B 
               
               
                   
                 7 days 
               
               
                   
                 slurry, 1 day 
                 white solid 
                 B 
               
               
                   
                 slurry, 1 day, dried 
                 white solid 
                 — 
               
               
                   
                 under N 2 , 3 days 
               
               
                 2,2,2- 
                 FE 
                 white, dendridic formations, 
                 E 
               
               
                 trifluoroethanol 
                   
                 birefringent 
               
               
                   
                 FE 
                 white, dendridic formations, 
                 E 
               
               
                   
                   
                 birefringent 
               
               
                 water 
                 FE 
                 white spherulites, birefringent 
                 G 
               
               
                   
                 FE 
                 tiny white spherulites of 
                 G 
               
               
                   
                   
                 needles, birefringent; white, 
               
               
                   
                   
                 morphology unknown, not 
               
               
                   
                   
                 birefringent 
               
               
                   
               
               
                   a FE = fast evaporation 
               
               
                 b. Sample analyzed in capillary as slurry 
               
            
           
         
       
     
     Form A was analyzed by NMR and thermal techniques (Table 9A,  FIG. 7 ,  FIG. 8 ). A weight loss of approximately 0.95% was observed in TG between 16 and 225° C. The DSC exhibited two small broad endotherms at approximately 58 and 95° C., probably due to loss of residual solvent, followed by a sharp endotherm at approximately 208° C., probably due to the melt. 
     
       
         
           
               
             
               
                 TABLE 9A 
               
             
            
               
                   
               
               
                 Characterization of Tosylate Salt Form A 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 A 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                 DSC a   
                 endo 58 (broad), 95 
               
               
                   
                   
                 (broad) 208 (56 J/g) 
               
               
                   
                 TGA b   
                 0.95 @ 16-225 
               
               
                   
                   
               
               
                   
                   a endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   b weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Form B resulted from fast evaporation in acetonitrile. No solvent was present in the material based on the proton NMR spectrum ( FIG. 9 ). The thermal data for Form B are included in Table 10A and shown in  FIG. 10 . The DSC thermogram exhibited a broad endotherm at approximately 63° C. followed by a sharp endotherm at approximately 205° C. most likely due to the melt ( FIG. 10 ). The broad endotherm was probably due to dehydration and was accompanied by a weight loss of approximately 1.65% between 18 to 100° C. in TG, which was calculated to be approximately 0.45 mmol of water. 
     
       
         
           
               
             
               
                 TABLE 10A 
               
             
            
               
                   
               
               
                 Characterization of Tosylate Salt, Form B 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 B 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                 DSC a   
                 endo 63 (broad), 205 (52 J/g) 
               
               
                   
                 TGA b   
                 1.65 @ 18-100 
               
               
                   
                   
               
               
                   
                   a endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   b weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Form C was obtained in slurry experiments in isopropanol after four and seven days. The thermal data for Form C are included in Table 11A and shown in  FIG. 12 . The DSC thermogram exhibited a broad endotherm at approximately 124° C. with a shoulder at 113° C. followed by an exotherm at approximately 165° C. and an endotherm at approximately 196° C., possibly due to the melt. The broad endotherm at 124° C. was accompanied by a stepwise weight loss of 13.11% in the range of 18 to 140° C. The weight loss was due to desolvation and corresponded to approximately 1.2 mmol of isopropanol. Approximately one mole of isopropanol per one mole of the compound was found based on the  1 H NMR spectrum ( FIG. 11 ). 
     
       
         
           
               
             
               
                 TABLE 11A 
               
             
            
               
                   
               
               
                 Characterization of Tosylate Salt, Form C 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 C 
               
               
                   
                   1 H NMR 
                 0.91 mole of isopropanol per 1 mole of 
               
               
                   
                   
                 compound 
               
               
                   
                 DSC b   
                 shoulder 113, endo 124, exo 165, endo 196 
               
               
                   
                 TGA c   
                 13.11@ 18-140 
               
               
                   
                   
               
               
                   
                   b endo = endotherm, exo = exotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   c weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Form D resulted from a slurry experiment in tetrahydrofuran after seven days. The characterization data for Form D are summarized in Table 12A. Peak shifts in the proton NMR indicated a different structure that was, nonetheless, related to the structure of the tosylate salt ( FIG. 13 ). The amount of material was insufficient for further characterization. Form D was not reproduced in a scale-up experiment. 
     
       
         
           
               
             
               
                 TABLE 12A 
               
             
            
               
                   
               
               
                 Characterization of Tosylate Salt, Form D 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 D 
               
               
                   
                   1 H NMR 
                 different structure 
               
               
                   
                   
               
            
           
         
       
     
     Form E was obtained in a fast evaporation experiment in 2,2,2-trifluoroethanol. The thermal data for Form E are included in Table 13A and shown in  FIG. 15 . The DSC thermogram exhibited three broad endotherms at approximately 67, 102, and 138° C. followed by a sharper intensive endotherm at approximately 199° C., likely due to the melt, and a small broad endotherm at 224° C. The first three endotherms were accompanied by a stepwise weight loss of 7.87% between 16 and 150° C. A residual amount of trifluoroethanol, approximately 0.143 mole per one mole of the compound, was found in the  1 H NMR spectrum ( FIG. 14 , Table 13A). The observed weight loss was probably due to both desolvation and dehydration (calculated to be approximately 0.4 mmol of 2,2,2-trifluoroethanol). 
     
       
         
           
               
             
               
                 TABLE 13A 
               
             
            
               
                   
               
               
                 Characterization of Tosylate Salt, Form E 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 E 
               
               
                   
                   1 H NMR 
                 0.143 mole of TFE a  per 1 mole of 
               
               
                   
                   
                 compound 
               
               
                   
                 DSC b   
                 endo 67 (broad), 102, 138, 199, 224 
               
               
                   
                 TGA c   
                 7.87 @ 16-150 
               
               
                   
                   
               
               
                   
                   a TFE = 2,2,2-trifluoroethanol 
               
               
                   
                   b endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   c weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Form F (also referred to as crystal modification X) was produced in slurry experiments in ethyl acetate after four and seven days. No solvent was present in the material based on the  1 H NMR spectrum ( FIG. 16 ). The thermal data for Form F are included in Table 14A and shown in  FIG. 17 . The DSC thermogram exhibited a broad endotherm at approximately 66° C. followed by a sharp endotherm at approximately 205° C., likely due to the melt. The broad endotherm accompanied by a weight loss of approximately 1.15% in the range of 17 to 100° C. in TG was possibly due to dehydration. The weight loss was calculated to be approximately 0.3 mmol of water. 
     
       
         
           
               
             
               
                 TABLE 14A 
               
             
            
               
                   
               
               
                 Characterization of Tosylate Salt, Form F 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 F 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                 DSC a   
                 endo 66 (broad), 205 (54 J/g) 
               
               
                   
                 TGA b   
                 1.15 @ 17-140 
               
               
                   
                   
               
               
                   
                   a endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   b weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Form G obtained from fast evaporation in water was likely a hydrate. The XRPD and proton NMR data for Form G are summarized in Table 15A (structure confirmed by NMR,  FIG. 18 ). 
     
       
         
           
               
             
               
                 TABLE 15A 
               
             
            
               
                   
               
               
                 Characterization of Tosylate Salt, Form G 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 G 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     Form H (also called crystal modification Y) was produced in a slurry experiment in tetrahydrofuran after four and seven days. The thermal data for Form H are included in Table 16A and shown in  FIG. 20 . The DSC thermogram exhibited a broad endotherm at approximately 115° C. with a shoulder at 127° C. followed by a small endotherm at approximately 186° C. The endotherm at 115° C. was accompanied by a stepwise weight loss of approximately 14.70% in the range of 16 to 145° C., probably due to desolvation (corresponded to approximately 1.15 mmol of tetrahydrofuran,). Approximately 0.7 mole of tetrahydrofuran per one mole of compound was found by  1 H NMR ( FIG. 19 ). 
     
       
         
           
               
             
               
                 TABLE 16A 
               
             
            
               
                   
               
               
                 Characterization of Tosylate Salt, Form H 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 H 
               
               
                   
                   1 H NMR 
                 0.7 mole of THF per 1 mole of compound 
               
               
                   
                 DSC b   
                 endo at 115, shoulder at 127, endo at 186 (small) 
               
               
                   
                 TGA c   
                 14.70 @ 16-145 
               
               
                   
                   
               
               
                   
                   b endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   c weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Results—Wellplate Salt Screen 
     Wellplate 1 
     Salt preparation results for wellplate 1 are summarized in Table 17A and Table 18A. The following acids were used in the screen: 
     acetic, 
     adipic, 
     citric, 
     gentisic, 
     glutaric, 
     glycolic, 
     L-malic. 
     The acids were dissolved in methanol and added to solutions of the freebase dissolved in acetone, methanol, methyl ethyl ketone, and tetrahydrofuran. Solids were obtained from slurry/fast evaporation experiments in the wells. 
     The free base (i.e. compound 2) was also dissolved in acetone, MeOH, MEK and THF) and solids obtained (well plate numbers H1, H2, H4, H5, H7, H8, H10 and H11 Table 17A). These experiments resulted in the amorphous form of compound 2. 
     
       
         
           
               
             
               
                 TABLE 17A 
               
               
                   
               
             
            
               
                 Wellplate Salt Preparation Attempts from Compound 2 
               
               
                 Plate 1; acids dissolved in methanol; ambient-temperature mix; 1:1equivalents acid/API 
               
               
                 with excess ac 
               
               
                   
               
            
           
           
               
               
               
            
               
                   
                 Observations b   
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 API 
                   
                   
                 11 days (sat 6 
                   
                 Well 
                 XRPD 
               
               
                 Acid 
                 Solvent a   
                 3 days 
                 B/E 
                 days/evaporated) 
                 B/E 
                 No. 
                 Results 
               
               
                   
               
               
                 citric 
                 acetone 
                 — 
                 — 
                 irregular plates 
                 Y 
                 C1 
                 low 
               
               
                   
                   
                   
                   
                 (caramel) 
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                 irregular plates 
                 Y 
                 C2 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 C3 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
                 MeOH 
                 — 
                 — 
                 wisps (caramel) 
                 Y 
                 C4 
                 low 
               
               
                   
                   
                   
                   
                   
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 N 
                 C5 
                 low 
               
               
                   
                   
                   
                   
                 (yellow) 
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 N 
                 C6 
                 low 
               
               
                   
                   
                   
                   
                 (white) 
                   
                   
                 crystalline 1 
               
               
                   
                 MEK 
                 — 
                 — 
                 unknown morphology 
                 N 
                 C7 
                 low 
               
               
                   
                   
                   
                   
                 (red) 
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                   
                   
                 C8 
                 low 
               
               
                   
                   
                   
                   
                   
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                   
                   
                 C9 
                 low 
               
               
                   
                   
                   
                   
                   
                   
                   
                 crystalline 1 
               
               
                   
                 THF 
                 — 
                 — 
                 needles (caramel) 
                 Y 
                 C10 
                 amorphous 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 C11 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 C12 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                 gentisic 
                 acetone 
                 — 
                 — 
                 needles (caramel) 
                 Y 
                 D1 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 D2 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 D3 
                 amorphous 
               
               
                   
                 MeOH 
                 dark 
                 N 
                 (yellow) 
                 N 
                 D4 
                 amorphous 
               
               
                   
                   
                 rings 
               
               
                   
                   
                 — 
                 — 
                   
                   
                 D5 
                 amorphous 
               
               
                   
                   
                 — 
                 — 
                   
                   
                 D6 
                 amorphous 
               
               
                   
                 MEK 
                 — 
                 — 
                 unknown morphology 
                 Y 
                 D7 
                 amorphous 
               
               
                   
                   
                   
                   
                 (orange) 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 D8 
                 amorphous 
               
               
                   
                   
                   
                   
                 (red) 
               
               
                   
                   
                   
                   
                 needles (black, red) 
                 Y 
                 D9 
                 amorphous 
               
               
                   
                 THF 
                 — 
                 — 
                 needles (caramel) 
                 Y 
                 D10 
                 amorphous 
               
               
                   
                   
                 glass 
                 N 
                 needles (caramel) 
                 Y 
                 D11 
                 amorphous 
               
               
                   
                   
                 glass 
                 N 
                 unknown morphology 
                 Y 
                 D12 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
               
            
           
           
               
            
               
                   a MeOH = methanol, MEK = methyl ethyl ketone, THF = tetrahydrofuran. 
               
               
                   b B = birefringence, E = extinction; samples observed under microscope with 
               
               
                 crossed polarized light; Y = yes, N = no. All wells exhibited dark rings upon 
               
               
                 final observation. Visual observations for color are given in parentheses. 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 acetic 
                 acetone 
                 — 
                 — 
                 (caramel) 
                 N 
                 A1 
                 amorphous 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 A2 
                 amorphous 
               
               
                   
                   
                   
                   
                 (brown, caramel) 
               
               
                   
                   
                   
                   
                 wisps (brown) 
                 Y 
                 A3 
                 crystalline 1 
               
               
                   
                 MeOH 
                 — 
                 — 
                 few needles (caramel) 
                 Y 
                 A4 
                 amorphous 
               
               
                   
                   
                   
                   
                 few wisps (yellow) 
                 Y 
                 A5 
                 amorphous 
               
               
                   
                   
                   
                   
                 few needles (caramel) 
                 Y 
                 A6 
                 crystalline 1 
               
               
                   
                 MEK 
                 — 
                 — 
                 unknown morphology 
                 Y 
                 A7 
                 amorphous 
               
               
                   
                   
                   
                   
                 (red) 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 A8 
                 amorphous 
               
               
                   
                   
                   
                   
                 (red) 
               
               
                   
                   
                   
                   
                 needles (red) 
                 Y 
                 A9 
                 amorphous 
               
               
                   
                 THF 
                 — 
                 — 
                 needles (caramel) 
                 Y 
                 A10 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 A11 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 A12 
                 amorphous 
               
               
                 adipic 
                 acetone 
                 — 
                 — 
                 irregular plates 
                 Y 
                 B1 
                 low 
               
               
                   
                   
                   
                   
                 (brown, caramel) 
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                 irregular plates 
                 Y 
                 B2 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 (brown) 
               
               
                   
                   
                   
                   
                 irregular plates 
                 Y 
                 B3 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 (brown) 
               
               
                   
                 MeOH 
                 — 
                 — 
                 unknown morphology 
                 Y 
                 B4 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 B5 
                 amorphous 
               
               
                   
                   
                   
                   
                 (yellow) 
               
               
                   
                   
                   
                   
                 few needles (yellow) 
                 Y 
                 B6 
                 crystalline 
               
               
                   
                   
                   
                   
                   
                   
                   
                 1 minus 
               
               
                   
                   
                   
                   
                   
                   
                   
                 peaks 
               
               
                   
                 MEK 
                 — 
                 — 
                 wisps (red) 
                 Y 
                 B7 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 B8 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 B9 
                 amorphous 
               
               
                   
                 THF 
                 — 
                 — 
                 unknown morphology 
                 Y 
                 B10 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
                   
                 B11 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 B12 
                 amorphous 
               
            
           
           
               
            
               
                   a MeOH = methanol, MEK = methyl ethyl ketone, THF = tetrahydrofuran. 
               
               
                   b B = birefringence, E = extinction; samples observed under microscope with 
               
               
                 crossed polarized light; Y = yes, N = no. All wells exhibited dark rings upon final 
               
               
                 observation. Visual observations for color are given in parentheses. 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 glutaric 
                 acetone 
                 — 
                 — 
                 irregular plates 
                 Y 
                 E1 
                 amorphous 
               
               
                   
                   
                   
                   
                 (brown, caramel) 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 E2 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 E3 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
                 MeOH 
                 — 
                 — 
                 (caramel) 
                 N 
                 E4 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
                 N 
                 E5 
                 amorphous 
               
               
                   
                   
                   
                   
                 (yellow) 
                 N 
                 E6 
                 amorphous 
               
               
                   
                 MEK 
                 — 
                 — 
                 (caramel) 
                 N 
                 E7 
                 amorphous 
               
               
                   
                   
                   
                   
                 needles (orange) 
                 Y 
                 E8 
                 amorphous 
               
               
                   
                   
                   
                   
                 wisps (red) 
                 Y 
                 E9 
                 amorphous 
               
               
                   
                 THF 
                 — 
                 — 
                 wisps (caramel) 
                 Y 
                 E10 
                 amorphous 
               
               
                   
                   
                   
                   
                 wisps (caramel) 
                 Y 
                 E11 
                 amorphous 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 E12 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                 glycolic 
                 acetone 
                 — 
                 — 
                 unknown morphology 
                 Y 
                 F1 
                 low 
               
               
                   
                   
                   
                   
                 (brown, caramel) 
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                 wisps (caramel) 
                 Y 
                 F2 
                 amorphous 
               
               
                   
                   
                   
                   
                 few irregular plates 
                 Y 
                 F3 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
                 MeOH 
                 — 
                 — 
                 (caramel) 
                 N 
                 F4 
                 amorphous 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 F5 
                 amorphous 
               
               
                   
                   
                   
                   
                 (yellow) 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 F6 
                 amorphous 
               
               
                   
                   
                   
                   
                 (yellow) 
               
               
                   
                 MEK 
                 — 
                 — 
                 unknown morphology 
                 Y 
                 F7 
                 amorphous 
               
               
                   
                   
                   
                   
                 (red) 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 F8 
                 amorphous 
               
               
                   
                   
                   
                   
                 (orange) 
               
               
                   
                   
                   
                   
                 unknown morphology 
                 Y 
                 F9 
                 amorphous 
               
               
                   
                   
                   
                   
                 (red) 
                   
                   
                 with peaks 
               
               
                   
                 THF 
                 glass 
                 N 
                 needles (caramel) 
                 Y 
                 F10 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                   
                   
                 F11 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                   
                   
                 F12 
                 amorphous 
               
            
           
           
               
            
               
                   a MeOH = methanol, MEK = methyl ethyl ketone, THF = tetrahydrofuran. 
               
               
                   b B = birefringence, E = extinction; samples observed under microscope with 
               
               
                 crossed polarized light; Y = yes, N = no. All wells exhibited dark rings upon final 
               
               
                 observation. Visual observations for color are given in parentheses. 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 L-malic 
                 acetone 
                 — 
                 — 
                 unknown 
                 Y 
                 G1 
                 amorphous 
               
               
                   
                   
                   
                   
                 morphology (brown, 
               
               
                   
                   
                   
                   
                 caramel) 
               
               
                   
                   
                   
                   
                 unknown 
                 Y 
                 G2 
                 amorphous 
               
               
                   
                   
                   
                   
                 morphology (brown, 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                 caramel) 
               
               
                   
                   
                   
                   
                 needles (brown, 
                 Y 
                 G3 
                 amorphous 
               
               
                   
                   
                   
                   
                 caramel) 
                   
                   
                 with peaks 
               
               
                   
                 MeOH 
                 — 
                 — 
                 few wisps (caramel) 
                 Y 
                 G4 
                 amorphous 
               
               
                   
                   
                 dark 
                 N 
                 prisms, needles 
                 Y 
                 G5 
                 crystalline 1 
               
               
                   
                   
                 rings 
                   
                 (caramel) 
               
               
                   
                   
                 — 
                 — 
                 unknown 
                 Y 
                 G6 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 morphology, needles 
               
               
                   
                   
                   
                   
                 (red) 
               
               
                   
                 MEK 
                 — 
                 — 
                 (red) 
                 N 
                 G7 
                 amorphous 
               
               
                   
                   
                   
                   
                 unknown 
                 Y 
                 G8 
                 amorphous 
               
               
                   
                   
                   
                   
                 morphology (red) 
               
               
                   
                   
                   
                   
                 prisms (singles), 
                 Y 
                 G9 
                 amorphous 
               
               
                   
                   
                   
                   
                 needles (red) 
                   
                   
                 with peaks 
               
               
                   
                 THF 
                 glass 
                 N 
                 wisps (caramel) 
                 Y 
                 G10 
                 amorphous 
               
               
                   
                   
                   
                   
                 unknown 
                 Y 
                 G11 
                 amorphous 
               
               
                   
                   
                   
                   
                 morphology 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
                   
                   
                   
                 wisps (caramel) 
                 Y 
                 G12 
                 amorphous 
               
               
                 none 
                 acetone 
                 — 
                 — 
                 unknown 
                 Y 
                 H1 
                 amorphous 
               
               
                   
                   
                   
                   
                 morphology 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
                   
                   
                   
                 needles (caramel) 
                 Y 
                 H2 
                 amorphous 
               
               
                   
                 MeOH 
                 — 
                 — 
                 needles (brown, 
                 Y 
                 H4 
                 amorphous 
               
               
                   
                   
                   
                   
                 caramel) 
               
               
                   
                   
                   
                   
                 (yellow) 
                 N 
                 H5 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                   
                 with peaks 
               
               
                   
                 MEK 
                 — 
                 — 
                 needles (red, 
                 Y 
                 H7 
                 amorphous 
               
               
                   
                   
                   
                   
                 caramel) 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                   
                 few needles 
                 Y 
                 H8 
                 amorphous 
               
               
                   
                   
                   
                   
                 (red, caramel) 
               
               
                   
                 THF 
                 — 
                 — 
                 unknown 
                 Y 
                 H10 
                 amorphous 
               
               
                   
                   
                   
                   
                 morphology 
                   
                 H11 
                 amorphous 
               
               
                   
                   
                   
                   
                 (caramel) 
               
               
                   
               
            
           
           
               
            
               
                   a MeOH = methanol, MEK = methyl ethyl ketone, THF = tetrahydrofuran. 
               
               
                   b B = birefringence, E = extinction; samples observed under microscope with 
               
               
                 crossed polarized light; Y = yes, N = no. Singles = well contained particles 
               
               
                 suitable for structure determination submission. All wells exhibited dark rings upon final 
               
               
                 observation. Visual observations for color are given in parentheses. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 18A 
               
             
            
               
                   
               
               
                 Summary of Well Plate Crystalline Forms 
               
            
           
           
               
               
               
               
            
               
                 Acid 
                 Solvent System b   
                 Well No. 
                 XRPD Result 
               
               
                   
               
               
                 acetic 
                 acetone, MeOH a   
                 A3 
                 crystalline 1 
               
               
                   
                 MeOH 
                 A6 
               
               
                   
                 MeOH:ACN 1:1 
                 A3 
               
               
                   
                 MeOH:EtOAc 1:1 
                 A6 
               
               
                 adipic 
                 acetone, MeOH a   
                 B2 
                 crystalline 1 
               
               
                   
                   
                 B3 
               
               
                   
                 MeOH:ACN 1:1 
                 B1 
               
               
                   
                   
                 B2 
               
               
                   
                   
                 B3 
               
               
                   
                 MeOH:EtOAc 1:1 
                 B5 
               
               
                   
                 acetone, MeOH a   
                 B1 
                 low crystalline 1 
               
               
                   
                 MeOH 
                 B6 
                 crystalline 1 minus 
               
               
                   
                 MeOH:EtOAc 1:1 
                 B6 
                 peaks 
               
               
                 citric 
                 acetone, MeOH a   
                 C2 
                 crystalline 1 
               
               
                   
                   
                 C3 
               
               
                   
                 MeOH:ACN 1:1 
                 C1 
               
               
                   
                   
                 C3 
               
               
                   
                 MeOH:EtOAc 1:1 
                 C4 
               
               
                   
                   
                 C5 
               
               
                   
                   
                 C6 
               
               
                   
                 acetone, MeOH a   
                 C1 
                 low crystalline 1 
               
               
                   
                 MeOH 
                 C4 
               
               
                   
                   
                 C5 
               
               
                   
                   
                 C6 
               
               
                   
                 MEK, MeOH a   
                 C7 
               
               
                   
                   
                 C8 
               
               
                   
                   
                 C9 
               
               
                 gentisic 
                 MeOH:EtOAc 1:1 
                 D5 
                 crystalline 1 
               
               
                   
                   
                 D6 
                 crystalline 2 
               
               
                 glutaric 
                 MeOH:ACN 1:1 
                 E1 
                 crystalline 1 
               
               
                   
                   
                 E2 
               
               
                   
                 MeOH:EtOAc 1:1 
                 E4 
               
               
                   
                   
                 E5 
               
               
                   
                   
                 E6 
               
               
                   
                 MeOH:ACN 1:1 
                 E3 
                 low crystalline 1 
               
               
                 glycolic 
                 MeOH:ACN 1:1 
                 F1 
                 crystalline 1 
               
               
                   
                 acetone, MeOH a   
                 F1 
                 low crystalline 1 
               
               
                   
                 MeOH:ACN 1:1 
                 F2 
               
               
                   
                   
                 F3 
               
               
                 HBr 
                 TFE, MeOH a   
                 A10 
                 crystalline 1 
               
               
                   
                   
                 A11 
               
               
                   
                   
                 A12 
               
               
                   
                 MeOH:EtOAc 1:1 
                 A5 
               
               
                   
                   
                 A6 
               
               
                   
                 MeOH:IPA 1:1 
                 A8 
               
               
                   
                 MeOH:toluene 1:1 
                 A10 
               
               
                   
                   
                 A11 
               
               
                   
                   
                 A12 
               
               
                   
                 acetone, MeOH a   
                 A2 
                 crystalline 2 
               
               
                   
                 MEK, MeOH a   
                 A7 
               
               
                   
                   
                 A8 
               
               
                   
                   
                 A9 
               
               
                   
                 MeOH:ACN 1:1 
                 A1 
               
               
                   
                   
                 A3 
               
               
                   
                 MeOH:IPA 1:1 
                 A9 
               
               
                   
                 MeOH:ACN 1:1 
                 A2 
                 low crystalline 2 
               
               
                 lactic 
                 MeOH:toluene 1:1 
                 B12 
                 crystalline 1 
               
               
                 maleic 
                 acetone, MeOH a   
                 C1 
                 crystalline 1 
               
               
                   
                   
                 C2 
               
               
                   
                 MeOH 
                 C4 
               
               
                   
                   
                 C5 
               
               
                   
                 MeOH:ACN 1:1 
                 C2 
               
               
                   
                 MeOH:EtOAc 1:1 
                 C5 
               
               
                   
                 acetone, MeOH a   
                 C3 
                 crystalline 1 + one peak 
               
               
                   
                 MeOH 
                 C6 
               
               
                   
                 MeOH:ACN 1:1 
                 C1 
               
               
                   
                   
                 C3 
               
               
                   
                 MeOH:EtOAc 1:1 
                 C4 
               
               
                   
                   
                 C6 
               
               
                   
                 MeOH:toluene 1:1 
                 C10 
               
               
                   
                   
                 C11 
               
               
                   
                   
                 C12 
               
               
                   
                 TFE, MeOH a   
                 C11 
                 low crystalline 1 
               
               
                 L-malic 
                 MeOH 
                 G5 
                 crystalline 1 
               
               
                   
                   
                 G6 
               
               
                   
                 MeOH:ACN 1:1 
                 G1 
               
               
                   
                   
                 G3 
               
               
                 phosphoric 
                 MeOH 
                 G4 
                 crystalline 1 
               
               
                   
                   
                 G6 
               
               
                   
                 TFE, MeOH a   
                 G10 
               
               
                   
                   
                 G11 
               
               
                   
                   
                 G12 
               
               
                   
                 MeOH:ACN 1:1 
                 G2 
               
               
                   
                   
                 G3 
               
               
                   
                 MeOH:EtOAc 1:1 
                 G4 
               
               
                   
                   
                 G5 
               
               
                   
                 MeOH:toluene 1:1 
                 G10 
               
               
                   
                   
                 G11 
               
               
                   
                   
                 G12 
               
               
                   
                 acetone, MeOH a   
                 G3 
                 crystalline 1 + peaks 
               
               
                   
                 MeOH:EtOAc 1:1 
                 G6 
               
               
                   
                 MeOH 
                 G5 
                 low crystalline 1 
               
               
                   
                 acetone, MeOH a   
                 G1 
                 crystalline 2 
               
               
                   
                   
                 G2 
               
               
                   
                 MeOH:ACN 1:1 
                 G1 
               
               
                   
                 MEK, MeOH a   
                 G7 
                 crystalline 3 
               
               
                   
                 MeOH:IPA 1:1 
                 G7 
               
               
                   
                 MEK, MeOH a   
                 G8 
                 crystalline 4 
               
               
                   
                 MeOH:IPA 1:1 
                 G8 
               
               
                 succinic 
                 acetone, MeOH a   
                 E1 
                 crystalline 1 
               
               
                   
                   
                 E2 
               
               
                   
                 MeOH 
                 E4 
               
               
                   
                   
                 E5 
               
               
                   
                   
                 E6 
               
               
                   
                 TFE, MeOH a   
                 E12 
               
               
                   
                 MeOH:ACN 1:1 
                 E1 
               
               
                   
                   
                 E2 
               
               
                   
                   
                 E3 
               
               
                   
                 MeOH:EtOAc 1:1 
                 E4 
               
               
                   
                   
                 E5 
               
               
                   
                   
                 E6 
               
               
                   
                 acetone, MeOH a   
                 E3 
                 low crystalline 1 
               
               
                   
                 TFE, MeOH a   
                 E10 
                 crystalline 2 
               
               
                   
                 MeOH:toluene 1:1 
                 E10 
               
               
                   
                   
                 E12 
               
               
                   
                   
                 E11 
                 crystalline 2 minus 
               
               
                   
                   
                   
                 peaks 
               
               
                 sulfuric 
                 acetone, MeOH a   
                 F2 
                 crystalline 1 
               
               
                   
                   
                 F3 
               
               
                   
                 MEK, MeOH a   
                 F8 
               
               
                   
                   
                 F9 
               
               
                   
                 TFE, MeOH a   
                 F10 
               
               
                   
                   
                 F11 
               
               
                   
                 MeOH:ACN 1:1 
                 F1 
               
               
                   
                   
                 F2 
               
               
                   
                   
                 F3 
               
               
                   
                 MeOH:IPA 1:1 
                 F7 
               
               
                   
                   
                 F9 
               
               
                   
                 MeOH:toluene 1:1 
                 F10 
               
               
                   
                   
                 F11 
               
               
                   
                   
                 F12 
               
               
                   
                 MeOH 
                 F4 
                 low crystalline 1 
               
               
                   
                 MEK, MeOH a   
                 F7 
               
               
                   
                 MeOH:EtOAc 1:1 
                 F4 
                 crystalline 1 minus 
               
               
                   
                   
                 F5 
                 peaks 
               
               
                   
                 MeOH:IPA 1:1 
                 F8 
               
               
                   
                 MeOH 
                 F6 
                 crystalline 2 
               
               
                   
                 MeOH:EtOAc 1:1 
                 F6 
                 crystalline 2 minus 
               
               
                   
                   
                   
                 peaks 
               
               
                   
                 acetone, MeOH a   
                 F1 
                 crystalline 3 
               
               
                   
                 MeOH 
                 F5 
                 crystalline 4 
               
               
                   
               
               
                   a Acids were dissolved in methanol then added to a solution containing freebase. The solvent that dissolved the freebase was the major component in the mixture. 
               
               
                   b ACN = acetonitrile, EtOAc = ethyl acetate, IPA = isopropanol, MeOH = methanol, MEK = methyl ethyl ketone, TFE = 2,2,2-trifluoroethanol. 
               
            
           
         
       
     
     Wellplate 2 
     Salt preparation results for wellplate 2 are summarized in Table 19A and Table 18A above. The following acids were used in the screen: 
     hydrobromic, 
     lactic, 
     maleic, 
     methanesulfonic, 
     succinic, 
     sulfuric, 
     phosphoric. 
     The acids were dissolved in methanol and added to solutions of compound 2 dissolved in acetone, methanol, methyl ethyl ketone, and 2,2,2-trifluoroethanol. Solids were obtained from slurry/fast evaporation experiments in the wells. 
     
       
         
           
               
             
               
                 TABLE 19A 
               
               
                   
               
             
            
               
                 Wellplate Salt Preparation Attempts from Compound 2 
               
               
                 Acids dissolved in methanol; ambient-temperature mix, 1:1 equivalents acid/API with excess 
               
               
                 acid (non-GMP) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 API 
                 Observations b   
                 Well 
                 XRPD 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Acid 
                 Solvent a   
                 3 days 
                 B/E 
                 8 days 
                 B/E 
                 No. 
                 Results 
               
               
                   
               
               
                 HBr 
                 acetone 
                 DR 
                 N 
                 yw, needles 
                 Y 
                 A1 
                 amorphous 
               
               
                   
                   
                 (clear at 8 d) 
                   
                 yw, UM 
                 Y 
                 A2 
                 crystalline 2 
               
               
                   
                   
                   
                   
                 white fibers 
                 Y 
                 A3 
                 amorphous 
               
               
                   
                   
                   
                   
                 UM 
                 N 
               
               
                   
                 MeOH 
                   
                   
                 white fibers 
                 N 
                 A4 
                 amorphous 
               
               
                   
                   
                   
                   
                 white needles 
                 Y 
                 A5 
                 amorphous 
               
               
                   
                   
                   
                   
                 white, UM 
                 Y 
                 A6 
                 amorphous 
               
               
                   
                 MEK c   
                 DR (yw) 
                 N 
                 OR needles 
                 Y 
                 A7 
                 crystalline 2 
               
               
                   
                   
                   
                   
                 UM 
                 N 
               
               
                   
                   
                   
                   
                 OR oil 
                 N 
                 A8 
                 crystalline 2 
               
               
                   
                   
                   
                   
                 OR, UM 
                 N 
                 A9 
                 crystalline 2 
               
               
                   
                 TFE 
                 DR, dark 
                 N 
                 off-white, UM 
                 partial 
                 A10 
                 crystalline 1 
               
               
                   
                   
                 chunks of 
                   
                   
                 partial 
                 A11 
                 crystalline 1 
               
               
                   
                   
                 UM 
                   
                   
                 N 
                 A12 
                 crystalline 1 
               
               
                   
                   
                 (white at 
               
               
                   
                   
                 8 d) 
               
               
                 lactic 
                 acetone 
                 DR, few 
                 Y 
                 yw fibers, UM 
                 Y 
                 B1 
                 amorphous 
               
               
                   
                   
                 platy 
                   
                 yw irregular 
                 Y 
                 B2 
                 amorphous 
               
               
                   
                   
                 particles 
                   
                 plates 
               
               
                   
                   
                 (yw) 
               
               
                   
                   
                 DR, platy 
                 Y 
                 yw, UM 
                 Y 
                 B3 
                 amorphous 
               
               
                   
                   
                 particles, 
               
               
                   
                   
                 specks (yw) 
               
               
                   
                 MeOH 
                 DR (clear at 
                 N 
                 off-white glass 
                 N 
                 B4 
                 amorphous 
               
               
                   
                   
                 8 d) 
                   
                 UM 
                 Y 
                   
                 with peaks 
               
               
                   
                   
                   
                   
                 clear oil 
                 N 
                 B5 
                 amorphous 
               
               
                   
                   
                   
                   
                 clear fibers, UM 
                 Y 
                 B6 
                 amorphous 
               
               
                   
                 MEK 
                 DR (yw) 
                 N 
                 OR glass 
                 N 
                 B7 
                 amorphous 
               
               
                   
                   
                   
                   
                 fibers 
                 Y 
               
               
                   
                   
                   
                   
                 OR glass, UM 
                 N 
                 B8 
                 amorphous 
               
               
                   
                   
                 DR (yw at 
                   
                 OR oil 
                 N 
                 B9 
                 amorphous 
               
               
                   
                   
                 3 d, OR at 
               
               
                   
                   
                 8 d) 
               
               
                   
                 TFE 
                 DR (clear at 
                 N 
                 clear glass, UM 
                 N 
                 B10 
                 amorphous 
               
               
                   
                   
                 8 d) 
                   
                 one fiber 
                 Y 
               
               
                   
                   
                   
                   
                 clear, UM 
                 Y 
                 B11 
                 amorphous 
               
               
                   
                   
                   
                   
                 glass 
                 N 
               
               
                   
                   
                   
                   
                 clear fibers 
                 Y 
                 B12 
                 amorphous 
               
               
                   
                   
                   
                   
                 glass, UM 
                 N 
               
            
           
           
               
            
               
                   a MeOH = methanol, MEK = methyl ethyl ketone, TFE = 2,2,2-trifluoroethanol. 
               
               
                   b B = birefringence, E = extinction; samples observed under microscope with crossed polarized 
               
               
                 light; DR = dark rings, d = days, yw = yellow, OR = orange, clear = colorless, UM = unknown 
               
               
                 morphology, Y = yes, N = no. Singles = well contained particles suitable for structure 
               
               
                 determination submission. All wells exhibited dark rings upon final observation. Visual 
               
               
                 observations for color. 
               
               
                   c Violet solution produced upon acid addition 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 maleic 
                 acetone 
                 DR (yw) 
                 N 
                 yw, UM 
                 N 
                 C1 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 fibers, UM 
                 Y 
               
               
                   
                   
                   
                   
                 yw spherulites 
                 Y 
                 C2 
                 crystalline 1 
               
               
                   
                   
                   
                   
                   
                   
                 C3 
                 crystalline 
               
               
                   
                   
                   
                   
                   
                   
                   
                 1 + one 
               
               
                   
                   
                   
                   
                   
                   
                   
                 peak 
               
               
                   
                 MeOH 
                 DR (clear at 
                 N 
                 yw spherulites, one 
                 Y 
                 C4 
                 crystalline 1 
               
               
                   
                   
                 8 d) 
                   
                 fiber 
               
               
                   
                   
                   
                   
                 white, UM 
                 N 
                 C5 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 clear spherulites, 
                 Y 
                 C6 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 one fiber 
                   
                   
                 1 + one 
               
               
                   
                   
                   
                   
                   
                   
                   
                 peak 
               
               
                   
                 MEK 
                 DR (yw) 
                 N 
                 OR glass, UM 
                 N 
                 C7 
                 amorphous 
               
               
                   
                   
                 DR, dark 
                 N 
                 OR oil 
                 N 
                 C8 
                 amorphous 
               
               
                   
                   
                 specks (yw) 
                   
                 UM 
                 Y 
                   
                 with peaks 
               
               
                   
                   
                 DR, oil 
                 N 
                 OR oil 
                 N 
                 C9 
                 amorphous 
               
               
                   
                   
                 (yw/pink) 
                   
                 UM 
                 Y 
               
               
                   
                   
                 (OR at 8 d) 
               
               
                   
                 TFE 
                 DR (white 
                 N 
                 pink spherulites 
                 Y 
                 C10 
                 amorphous 
               
               
                   
                   
                 at 8 d) 
                   
                 white spherulites 
                 Y 
                 C11 
                 low 
               
               
                   
                   
                   
                   
                   
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                 white spherulites, 
                 Y 
                 C12 
                 amorphous 
               
               
                   
                   
                   
                   
                 needles 
               
               
                 methane- 
                 acetone 
                 DR (clear at 
                 N 
                 clear glass, UM 
                 N 
                 D1 
                 amorphous 
               
               
                 sulfonic 
                   
                 8 d) 
                   
                 fibers 
                 Y 
               
               
                   
                   
                   
                   
                 yw fibers 
                 Y 
                 D2 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 D3 
                 amorphous 
               
               
                   
                 MeOH 
                   
                   
                 clear glass, UM 
                 N 
                 D4 
                 amorphous 
               
               
                   
                   
                   
                   
                 clear fibers, needles 
                 Y 
                 D5 
                 amorphous 
               
               
                   
                   
                   
                   
                 clear glass 
                 N 
                 D6 
                 amorphous 
               
               
                   
                   
                   
                   
                 UM 
                 Y 
                   
                 with peaks 
               
               
                   
                 MEK c   
                 DR (yw) 
                 N 
                 yw oil 
                 N 
                 D7 
                 amorphous 
               
               
                   
                   
                   
                   
                 needles 
                 Y 
               
               
                   
                   
                 DR, oil (yw 
                 N 
                 violet oil 
                 N 
                 D8 
                 amorphous 
               
               
                   
                   
                 at 8 d) 
               
               
                   
                   
                 DR, dark 
                 N 
                 brown oil 
                 N 
                 D9 
                 amorphous 
               
               
                   
                   
                 specks 
                   
                 UM 
                 Y 
               
               
                   
                   
                 (pink at 8 d) 
               
               
                   
                 TFE 
                 DR (clear at 
                 N 
                 yw oil 
                 N 
                 D10 
                 amorphous 
               
               
                   
                   
                 8 d) 
                   
                 fibers, UM 
                 Y 
               
               
                   
                   
                   
                   
                 yw oil, UM 
                 N 
                 D11 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 D12 
                 amorphous 
               
            
           
           
               
            
               
                   a MeOH = methanol, MEK = methyl ethyl ketone, TFE = 2,2,2-trifluoroethanol. 
               
               
                   b B = birefringence, E = extinction; samples observed under microscope with crossed polarized 
               
               
                 light; DR = dark rings, d = days, yw = yellow, OR = orange, clear = colorless, UM = unknown 
               
               
                 morphology, Y = yes, N = no. Singles = well contained particles suitable for structure 
               
               
                 determination submission. All wells exhibited dark rings upon final observation. Visual 
               
               
                 observations for color. 
               
               
                   c Violet solution produced upon acid addition 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 succinic 
                 acetone 
                 DR, (yw) 
                 N 
                 caramel-colored, 
                 N 
                 E1 
                 crystalline 1 
               
               
                   
                   
                 (OR, yw at 
                   
                 UM 
               
               
                   
                   
                 8 d) 
               
               
                   
                   
                 DR (yw) 
                 N 
                   
                   
                 E2 
                 crystalline 1 
               
               
                   
                   
                 DR (yw) 
                 N 
                 caramel-colored, 
                 Y 
                 E3 
                 low 
               
               
                   
                   
                 (OR, yw at 
                   
                 fibers, UM 
                   
                   
                 crystalline 1 
               
               
                   
                   
                 8 d) 
               
               
                   
                 MeOH 
                 DR (clear at 
                 N 
                 yw, UM 
                 N 
                 E4 
                 crystalline 1 
               
               
                   
                   
                 8 d) 
                   
                 needles 
                 Y 
               
               
                   
                   
                   
                   
                 off-white blades 
                 Y 
                 E5 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 pink blades 
                 Y 
                 E6 
                 crystalline 1 
               
               
                   
                 MEK 
                 DR (yw) 
                 N 
                 red, UM 
                 N 
                 E7 
                 amorphous 
               
               
                   
                   
                   
                   
                 fibers 
                 Y 
               
               
                   
                   
                 DR, oil (yw) 
                 N 
                 red oil 
                 N 
                 E8 
                 amorphous 
               
               
                   
                   
                   
                   
                 UM 
                 Y 
               
               
                   
                   
                 DR, oil 
                 N 
                 red oil 
                 N 
                 E9 
                 amorphous 
               
               
                   
                   
                 (yw/pink) 
                   
                 UM 
                 Y 
               
               
                   
                   
                 (OR at 8 d) 
               
               
                   
                 TFE 
                 DR (pink, 
                 N 
                 pink spherulites, 
                 Y 
                 E10 
                 crystalline 2 
               
               
                   
                   
                 off-white at 
                   
                 needles 
               
               
                   
                   
                 8 d) 
               
               
                   
                   
                 DR (off- 
                 N 
                 white spherulites 
                 Y 
                 E11 
                 low 
               
               
                   
                   
                 white at 8 d) 
                   
                 of very fine fibers 
                   
                   
                 crystalline 1 
               
               
                   
                   
                 DR (clear at 
                 N 
                 white, UM 
                 N 
                 E12 
                 crystalline 1 
               
               
                   
                   
                 8 d) 
               
               
                 H 2 SO 4   
                 acetone 
                 DR (yw) 
                 N 
                 OR, UM 
                 partial 
                 F1 
                 crystalline 3 
               
               
                   
                   
                 DR, few 
                 Y 
                 yw, UM 
                 N 
                 F2 
                 crystalline 1 
               
               
                   
                   
                 large 
               
               
                   
                   
                 hexagonal 
               
               
                   
                   
                 plates 
               
               
                   
                   
                 (singles) 
               
               
                   
                   
                 (yw) 
               
               
                   
                   
                 DR (yw) 
                 N 
                 yw irregular 
                 Y 
                 F3 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 plates 
               
               
                   
                 MeOH 
                 DR 
                 N 
                 clear, UM 
                 Y 
                 F4 
                 low 
               
               
                   
                   
                 (clear at 8 d) 
                   
                   
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                   
                   
                 partial 
                 F5 
                 crystalline 4 
               
               
                   
                   
                   
                   
                   
                 Y 
                 F6 
                 crystalline 2 
               
               
                   
                 MEK 
                 DR (yw) 
                 N 
                 OR, UM 
                 Y 
                 F7 
                 low 
               
               
                   
                   
                   
                   
                   
                   
                   
                 crystalline 1 
               
               
                   
                   
                 DR, oil (yw) 
                 N 
                 brown needles, 
                 Y 
                 F8 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 UM 
               
               
                   
                   
                 DR, oil 
                 N 
                 OR, UM 
                 Y 
                 F9 
                 crystalline 1 
               
               
                   
                   
                 (pink) 
               
               
                   
                   
                 (OR at 8 d) 
               
               
                   
                 TFE 
                 dark, UM 
                 N 
                 pink blades 
                 Y 
                 F10 
                 crystalline 1 
               
               
                   
                   
                 (pink at 8 d) 
               
               
                   
                   
                 dark, UM 
                   
                 white blades 
                 Y 
                 F11 
                 crystalline 1 
               
               
                   
                   
                 (off-white at 
               
               
                   
                   
                 8 d) 
               
               
                   
                   
                 dark, UM 
                   
                 white fibers, 
                 Y 
                 F12 
                 amorphous 
               
               
                   
                   
                 (white at 8 d) 
                   
                 needles 
               
            
           
           
               
            
               
                   a MeOH = methanol, MEK = methyl ethyl ketone, TFE = 2,2,2-trifluoroethanol. 
               
               
                   b B = birefringence, E = extinction; samples observed under microscope with crossed polarized 
               
               
                 light; DR = dark rings, d = days, yw = yellow, OR = orange, clear = colorless, UM = unknown 
               
               
                 morphology, Y = yes, N = no. Singles = well contained particles suitable for structure 
               
               
                 determination submission. All wells exhibited dark rings upon final observation. Visual 
               
               
                 observations for color. 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 H 3 PO 4   
                 acetone 
                 DR, few 
                 Y 
                 yw, UM 
                 N 
                 G1 
                 crystalline 2 
               
               
                   
                   
                 platy 
               
               
                   
                   
                 particles 
               
               
                   
                   
                 (yw) 
               
               
                   
                   
                 DR (yw) 
                 N 
                   
                   
                 G2 
                 crystalline 2 
               
               
                   
                   
                 dark solids 
                 N 
                   
                   
                 G3 
                 crystalline 
               
               
                   
                   
                 of UM (yw) 
                   
                   
                   
                   
                 1 + peaks 
               
               
                   
                 MeOH 
                 DR (yw at 
                 N 
                 off-white, UM 
                 partial 
                 G4 
                 crystalline 1 
               
               
                   
                   
                 8 d) 
               
               
                   
                   
                 DR (white 
                 N 
                 white blades, 
                 Y 
                 G5 
                 low 
               
               
                   
                   
                 at 8 d) 
                   
                 UM 
                   
                   
                 crystalline 1 
               
               
                   
                   
                 DR, rosette 
                 Y 
                 white, UM 
                 N 
                 G6 
                 crystalline 1 
               
               
                   
                   
                 clusters of 
                   
                 needles 
                 Y 
               
               
                   
                   
                 fine needles 
               
               
                   
                   
                 (white at 8 d) 
               
               
                   
                 MEK 
                 DR, oil (yw) 
                 N 
                 red, UM 
                 N 
                 G7 
                 crystalline 3 
               
               
                   
                   
                 (OR at 8 d) 
                 N 
                   
                 partial 
                 G8 
                 crystalline 4 
               
               
                   
                   
                 dark solids 
                 N 
                 red oil, UM 
                 N 
                 G9 
                 amorphous 
               
               
                   
                   
                 of UM 
                   
                   
                   
                   
                 with peaks 
               
               
                   
                   
                 (pink) 
               
               
                   
                   
                 (red at 8 d) 
               
               
                   
                 TFE c   
                 dark solids 
                 N 
                 off-white, UM 
                 N 
                 G10 
                 crystalline 1 
               
               
                   
                   
                 of UM (off- 
                   
                 needles 
                 Y 
               
               
                   
                   
                 white at 8 d) 
                   
                 white, UM 
                 N 
                 G11 
                 crystalline 1 
               
               
                   
                   
                   
                   
                 needles 
                 Y 
               
               
                   
                   
                 dark solids 
                   
                 white, UM 
                 N 
                 G12 
                 crystalline 1 
               
               
                   
                   
                 of UM 
                   
                 needles 
                 Y 
               
               
                   
                   
                 (white at 8 d) 
               
               
                 none 
                 acetone 
                 DR, dark 
                 N 
                 yw glass 
                 N 
                 H1 
                 amorphous 
               
               
                   
                   
                 chunks of 
                   
                 UM 
                 Y 
               
               
                   
                   
                 UM (yw) 
                   
                 yw glass 
                 N 
                 H2 
                 amorphous 
               
               
                   
                   
                   
                   
                 UM, one fiber 
                 Y 
               
               
                   
                 MeOH 
                 DR (clear at 
                 N 
                 clear fibers, UM 
                 Y 
                 H4 
                 amorphous 
               
               
                   
                   
                 8 d) 
                   
                 clear glass 
                 N 
                 H5 
                 amorphous 
               
               
                   
                   
                   
                   
                 UM 
                 Y 
               
               
                   
                 MEK 
                 DR, platy 
                 Y 
                 OR blades, 
                 Y 
                 H7 
                 amorphous 
               
               
                   
                   
                 particles, 
                   
                 irregular plates 
               
               
                   
                   
                 specks (red) 
               
               
                   
                   
                 (yw at 8 d) 
               
               
                   
                   
                 DR, oil (yw) 
                 N 
                 OR oil 
                 N 
                 H8 
                 amorphous 
               
               
                   
                   
                   
                   
                 needles, UM 
                 Y 
               
               
                   
                   
                 DR, oil (yw) 
                 N 
                 OR oil 
                 N 
                 H9 
                 amorphous 
               
               
                   
                   
                   
                   
                 UM 
                 Y 
               
               
                   
                 TFE 
                 DR (clear at 
                 N 
                 clear glass 
                 N 
                 H10 
                 amorphous 
               
               
                   
                   
                 8 d) 
                   
                 UM 
                 Y 
               
               
                   
                   
                   
                   
                 clear glass 
                 N 
                 H11 
                 amorphous 
               
               
                   
               
            
           
           
               
            
               
                   a MeOH = methanol, MEK = methyl ethyl ketone, TFE = 2,2,2-trifluoroethanol. 
               
               
                   b B = birefringence, E = extinction; samples observed under microscope with crossed polarized 
               
               
                 light; DR = dark rings, d = days, yw = yellow, OR = orange, clear = colorless, UM = unknown 
               
               
                 morphology, Y = yes, N = no. Singles = well contained particles suitable for structure 
               
               
                 determination submission. All wells exhibited dark rings upon final observation. Visual 
               
               
                 observations for color. 
               
               
                   c White precipitate produced upon acid addition. 
               
            
           
         
       
     
     Recrystallization of Salts in Wellplates 
     Wellplate 3 
     Recrystallization of wellplate 3 was conducted using solvent/antisolvent evaporation. The solids in wells were dissolved in methanol. Acetonitrile, ethyl acetate, 1-propanol, and toluene were used as the antisolvents. The wells with sufficient amounts of non-glassy solids were analyzed by XRPD and the results are summarized in Table 20A and Table 18A above. 
     
       
         
           
               
             
               
                 TABLE 20A 
               
             
            
               
                   
               
               
                 Recrystallization of Wellplate 3 
               
               
                 to all wells methanol was added; solvent:antisolvent 1:1 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Anti- 
                   
                   
                   
                 XRPD 
               
               
                 Acid 
                 Solvent a   
                 solvent b   
                 Observations 
                 B c   
                 Well No. 
                 Results 
               
               
                   
               
               
                 acetic 
                 MeOH 
                 ACN 
                 dark brown ring, 
                 N 
                 A1 
                 — 
               
               
                   
                   
                   
                 broken glass 
               
               
                   
                   
                   
                 dark brown ring, 
                 N 
                 A2 
                 — 
               
               
                   
                   
                   
                 glass 
               
               
                   
                   
                   
                 morphology 
                 Y 
                 A3 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 EtOAc 
                 a few needles 
                 Y 
                 A4 
                 — 
               
               
                   
                   
                   
                 glassy solid 
                 N 
                 A5 
                 — 
               
               
                   
                   
                   
                 morphology 
                 N 
                 A6 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 1-PrOH 
                 glassy solid 
                 N 
                 A7 
                 — 
               
               
                   
                   
                   
                 glassy solid 
                 N 
                 A8 
                 — 
               
               
                   
                   
                   
                 glassy solid 
                 N 
                 A9 
                 — 
               
               
                   
                   
                 toluene 
                 glassy solid 
                 N 
                 A10 
                 — 
               
               
                   
                   
                   
                 Morphology 
                 N 
                 A11 
                 — 
               
               
                   
                   
                   
                 unknown, a few 
               
               
                   
                   
                   
                 birefringent particles 
               
               
                   
                   
                   
                 glassy solid 
                 N 
                 A12 
                 — 
               
               
                 adipic 
                 MeOH 
                 ACN 
                 morphology 
                 N 
                 B1 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 morphology 
                 N 
                 B2 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 morphology 
                 N 
                 B3 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 EtOAc 
                 dark brown circle 
                 N 
                 B4 
                 — 
               
               
                   
                   
                   
                 morphology 
                 Part. Y 
                 B5 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 morphology 
                 Part. Y 
                 B6 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 minus peaks 
               
               
                   
                   
                 1-PrOH 
                 glassy solid with a 
                 N 
                 B7 
                 — 
               
               
                   
                   
                   
                 few birefringent 
               
               
                   
                   
                   
                 particles 
               
               
                   
                   
                   
                 glassy solid with a 
                 N 
                 B8 
                 — 
               
               
                   
                   
                   
                 few birefringent 
               
               
                   
                   
                   
                 particles 
               
               
                   
                   
                   
                 glassy solid 
                 N 
                 B9 
                 — 
               
               
                   
                   
                 toluene 
                 glassy solid 
                 N 
                 B10 
                 — 
               
               
                   
                   
                   
                 Glassy solid 
                 N 
                 B11 
                 — 
               
               
                   
                   
                   
                 Morphology 
                 Y 
                   
                 — 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 glassy solid with a 
                 N 
                 B12 
                 — 
               
               
                   
                   
                   
                 few birefringent 
               
               
                   
                   
                   
                 particles 
               
               
                 citric 
                 MeOH 
                 ACN 
                 light brown, 
                 N 
                 C1 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 light brown, 
                 N 
                 C2 
                 — 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 brown, morphology 
                 part. Y 
                 C3 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 EtOAc 
                 light brown, 
                 N 
                 C4 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 yellow plates 
                 Y 
                 C5 
                 crystalline 1 
               
               
                   
                   
                   
                 orange, morphology 
                 N 
                 C6 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 1-PrOH 
                 dark brown solid 
                 N 
                 C7 
                 — 
               
               
                   
                   
                   
                 brown, morphology 
                 N 
                 C8 
                 — 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 dark brown solid 
                 N 
                 C9 
                 — 
               
               
                   
                   
                 toluene 
                 light brown, glass 
                 N 
                 C10 
                 — 
               
               
                   
                   
                   
                 light brown, glass 
                 N 
                 C11 
                 — 
               
               
                   
                   
                   
                 light brown, glass 
                 N 
                 C12 
                 — 
               
               
                 gentisic 
                 MeOH 
                 ACN 
                 dark brown, glass 
                 N 
                 D1 
                 — 
               
               
                   
                   
                   
                 dark brown, glass 
                 N 
                 D2 
                 — 
               
               
                   
                   
                   
                 dark brown, glass 
                 N 
                 D3 
                 — 
               
               
                   
                   
                 EtOAc 
                 dark brown, glass 
                 N 
                 D4 
                 — 
               
               
                   
                   
                   
                 yellow solid 
                 N 
                 D5 
                 crystalline 1 
               
               
                   
                   
                   
                 light brown, stacked 
                 Y 
                 D6 
                 crystalline 2 
               
               
                   
                   
                   
                 plates 
               
               
                   
                   
                 1-PrOH 
                 clear, glass 
                 N 
                 D7 
                 — 
               
               
                   
                   
                   
                 clear brown, glass 
                 N 
                 D8 
                 — 
               
               
                   
                   
                   
                 clear brown, glass 
                 N 
                 D9 
                 — 
               
               
                   
                   
                 toluene 
                 clear brown, glass 
                 N 
                 D10 
                 — 
               
               
                   
                   
                   
                 clear brown, glass 
                 N 
                 D11 
                 — 
               
               
                   
                   
                   
                 clear brown, glass 
                 N 
                 D12 
                 — 
               
               
                 glutaric 
                 MeOH 
                 ACN 
                 dark brown, morphology 
                 Part. Y 
                 E1 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 dark brown, morphology 
                 Part. Y 
                 E2 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 dark brown, morphology 
                 Part. Y 
                 E3 
                 low 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 crystalline 1 
               
               
                   
                   
                 EtOAc 
                 dark brown, morphology 
                 Part. Y 
                 E4 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 orange, morphology 
                 N 
                 E5 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 orange, morphology 
                 Part. Y 
                 E6 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 1-PrOH 
                 clear brown, glass 
                 N 
                 E7 
                 — 
               
               
                   
                   
                   
                 clear brown, glass 
                 N 
                 E8 
                 — 
               
               
                   
                   
                   
                 clear brown, glass 
                 N 
                 E9 
                 — 
               
               
                   
                   
                 toluene 
                 dark brown, glass 
                 N 
                 E10 
                 — 
               
               
                   
                   
                   
                 dark brown, glass 
                 N 
                 E11 
                 — 
               
               
                   
                   
                   
                 dark brown, glass 
                 N 
                 E12 
                 — 
               
               
                 glycolic 
                 MeOH 
                 ACN 
                 brown, morphology 
                 N 
                 F1 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 brown, morphology 
                 N 
                 F2 
                 low 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 crystalline 1 
               
               
                   
                   
                   
                 brown, morphology 
                 N 
                 F3 
                 low 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 crystalline 1 
               
               
                   
                   
                 EtOAc 
                 brown, morphology 
                 N 
                 F4 
                 — 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 orange, morphology 
                 N 
                 F5 
                 — 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 orange, morphology 
                 N 
                 F6 
                 — 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 1-PrOH 
                 dark brown, morphology 
                 N 
                 F7 
                 — 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 small amount of dark 
                 N 
                 F8 
                 — 
               
               
                   
                   
                   
                 brown, morphology 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 small amount of dark 
                 N 
                 F9 
                 — 
               
               
                   
                   
                   
                 brown, morphology 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 toluene 
                 glass and some 
                 N 
                 F10 
                 — 
               
               
                   
                   
                   
                 birefringent particles 
               
               
                   
                   
                   
                 brown, glass 
                 N 
                 F11 
                 — 
               
               
                   
                   
                   
                 brown, glass 
                 N 
                 F12 
                 — 
               
               
                 L-malic 
                 MeOH 
                 ACN 
                 brown, morphology 
                 Part. Y 
                 G1 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 brown, morphology 
                 Part. Y 
                 G2 
                 — 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 brown, morphology 
                 Part. Y 
                 G3 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 EtOAc 
                 brown solid 
                 N 
                 G4 
                 — 
               
               
                   
                   
                   
                 brown solid 
                 N 
                 G5 
                 — 
               
               
                   
                   
                   
                 brown solid 
                 N 
                 G6 
                 — 
               
               
                   
                   
                 1-PrOH 
                 brown glass 
                 N 
                 G7 
                 — 
               
               
                   
                   
                   
                 clear glass 
                 N 
                 G8 
                 — 
               
               
                   
                   
                   
                 brown glass 
                 N 
                 G9 
                 — 
               
               
                   
                   
                 toluene 
                 clear brown glass 
                 N 
                 G10 
                 — 
               
               
                   
                   
                   
                 brown, morphology 
                 Y 
                 G11 
                 amorphous 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                 clear brown glass 
                 N 
                 G12 
                 — 
               
               
                 none 
                 MeOH 
                 ACN 
                 clear brown glass 
                 N 
                 H1 
                 — 
               
               
                   
                   
                   
                 clear brown glass 
                 N 
                 H2 
                 — 
               
               
                   
                   
                 EtOAc 
                 clear brown glass 
                 N 
                 H4 
                 — 
               
               
                   
                   
                   
                 clear brown glass 
                 N 
                 H5 
                 — 
               
               
                   
                   
                 1-PrOH 
                 clear glass 
                 N 
                 H7 
                 — 
               
               
                   
                   
                   
                 clear glass 
                 N 
                 H8 
                 — 
               
               
                   
                   
                 toluene 
                 dark brown glass 
                 N 
                 H10 
                 — 
               
               
                   
                   
                   
                 dark brown glass 
                 N 
                 H11 
                 — 
               
               
                   
               
               
                   a MeOH = methanol. 
               
               
                   b ACN = acetonitrile, EtOAc = ethyl acetate, 1-PrOH = 1-propanol. 
               
               
                   c B = birefringence, samples observed under microscope with crossed polarized light; Y = yes, N = no, Part. = partial. 
               
            
           
         
       
     
     Wellplate 4 
     Recrystallization of wellplate 3 was conducted using solvent/antisolvent evaporation. The solids in wells were dissolved in methanol. Acetonitrile, ethyl acetate, 1-propanol, and toluene were used as the antisolvents. The wells with sufficient amounts of non-glassy solids were analyzed by XRPD and the results are summarized in Table 21A and Table 18A above. 
     
       
         
           
               
             
               
                 TABLE 21A 
               
             
            
               
                   
               
               
                 Recrystallization of Wellplate 4 
               
               
                 to all wells methanol was added; solvent:antisolvent 1:1 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Anti- 
                   
                   
                 Well 
                 XRPD 
               
               
                 Acid 
                 Solvent a   
                 solvent b   
                 Observations 
                 B/E c   
                 No. 
                 Results 
               
               
                   
               
               
                 HBr 
                 MeOH 
                 ACN 
                 orange, morphology unknown 
                 partial 
                 A1 
                 crystalline 2 
               
               
                   
                   
                   
                 yellow fibers 
                 Y 
                 A2 
                 low 
               
               
                   
                   
                   
                   
                   
                   
                 crystalline 2 
               
               
                   
                   
                   
                 yellow needles 
                 Y 
                 A3 
                 crystalline 2 
               
               
                   
                   
                 EtOAc 
                 off-white, morphology 
                 N 
                 A4 
                 amorphous 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                 fibers, morphology unknown 
                 Y 
               
               
                   
                   
                   
                 off-white, morphology 
                 N 
                 A5 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 off-white, morphology 
                 partial 
                 A6 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 IPA 
                 colorless fibers 
                 Y 
                 A7 
                 amorphous 
               
               
                   
                   
                   
                 caramel-colored, morphology 
                 N 
                 A8 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 caramel-colored, morphology 
                 Y 
                 A9 
                 crystalline 2 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 toluene 
                 yellow, morphology unknown 
                 N 
                 A10 
                 crystalline 1 
               
               
                   
                   
                   
                 yellow, morphology unknown 
                 N 
                 A11 
                 crystalline 1 
               
               
                   
                   
                   
                 yellow, morphology unknown 
                 N 
                 A12 
                 crystalline 1 
               
               
                 lactic 
                 MeOH 
                 ACN 
                 yellow glass 
                 N 
                 B1 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 yellow glass 
                 N 
                 B2 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 yellow irregular plates and 
                 Y 
                 B3 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                 EtOAc 
                 colorless glass 
                 N 
                 B4 
                 amorphous 
               
               
                   
                   
                   
                 one fiber 
                 Y 
               
               
                   
                   
                   
                 colorless glass 
                 N 
                 B5 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 colorless fibers 
                 Y 
                 B6 
                 amorphous 
               
               
                   
                   
                 IPA 
                 off-white, morphology 
                 partial 
                 B7 
                 amorphous 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 off-white, morphology 
                 N 
                 B8 
                 amorphous 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 off-white, morphology 
                 partial 
                 B9 
                 amorphous 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 toluene 
                 colorless glass 
                 N 
                 B10 
                 amorphous 
               
               
                   
                   
                   
                 one fiber 
                 Y 
               
               
                   
                   
                   
                 colorless oil 
                 N 
                 B11 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
                   
                 with peaks 
               
               
                   
                   
                   
                 white, morphology unknown 
                 N 
                 B12 
                 crystalline 1 
               
               
                 maleic 
                 MeOH 
                 ACN 
                 orange, morphology 
                 N 
                 C1 
                 crystalline 1 + 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 one peak 
               
               
                   
                   
                   
                 caramel-colored, 
                 N 
                 C2 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 caramel-colored, 
                 N 
                 C3 
                 crystalline 1 + 
               
               
                   
                   
                   
                 morphology unknown 
                   
                   
                 one peak 
               
               
                   
                   
                 EtOAc 
                 yellow, morphology 
                 N 
                 C4 
                 crystalline 1 + 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 one peak 
               
               
                   
                   
                   
                 off-white, morphology 
                 N 
                 C5 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 pink, morphology unknown 
                 partial 
                 C6 
                 crystalline 1 + 
               
               
                   
                   
                   
                   
                   
                   
                 one peak 
               
               
                   
                   
                 IPA 
                 caramel-colored glass 
                 N 
                 C7 
                 amorphous 
               
               
                   
                   
                   
                 blades 
                 Y 
               
               
                   
                   
                   
                 caramel-colored glass 
                 N 
                 C8 
                 amorphous 
               
               
                   
                   
                   
                 blades 
                 Y 
               
               
                   
                   
                   
                 caramel-colored glass 
                 N 
                 C9 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                 toluene 
                 pink, morphology unknown 
                 N 
                 C10 
                 crystalline 1 + 
               
               
                   
                   
                   
                   
                   
                   
                 one peak 
               
               
                   
                   
                   
                 off-white, morphology 
                 N 
                 C11 
                 crystalline 1 + 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 one peak 
               
               
                   
                   
                   
                 white, morphology 
                 N 
                 C12 
                 crystalline 1 + 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 one peak 
               
               
                 methane- 
                 MeOH 
                 ACN 
                 yellow, glass 
                 N 
                 D1 
                 amorphous 
               
               
                 sulfonic 
                   
                   
                 fibers 
                 Y 
               
               
                   
                   
                   
                 yellow glass 
                 N 
                 D2 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 yellow glass 
                 N 
                 D3 
                 amorphous 
               
               
                   
                   
                   
                 fibers 
                 N 
               
               
                   
                   
                 EtOAc 
                 yellow glass 
                 N 
                 D4 
                 amorphous 
               
               
                   
                   
                   
                 yellow glass 
                 N 
                 D5 
                 amorphous 
               
               
                   
                   
                   
                 fibers 
                 Y 
               
               
                   
                   
                   
                 yellow glass 
                 N 
                 D6 
                 amorphous 
               
               
                   
                   
                   
                 fibers 
                 Y 
               
               
                   
                   
                 IPA 
                 colorless glass 
                 N 
                 D7 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 yellow oil 
                 N 
                 D8 
                 amorphous 
               
               
                   
                   
                   
                 yellow oil 
                 N 
                 D9 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                 toluene 
                 orange glass 
                 N 
                 D10 
                 amorphous 
               
               
                   
                   
                   
                 red glass and morphology 
                 N 
                 D11 
                 amorphous 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 with peaks 
               
               
                   
                   
                   
                 orange glass 
                 N 
                 D12 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 with peaks 
               
               
                 succinic 
                 MeOH 
                 ACN 
                 caramel-colored, 
                 Y 
                 E1 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 caramel-colored, 
                 partial 
                 E2 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 caramel-colored, 
                 partial 
                 E3 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                 EtOAc 
                 off-white, morphology 
                 N 
                 E4 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 off-white, morphology 
                 N 
                 E5 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 blades 
                 Y 
               
               
                   
                   
                   
                 pink, morphology unknown 
                 N 
                 E6 
                 crystalline 1 
               
               
                   
                   
                 IPA 
                 brown glass 
                 N 
                 E7 
                 amorphous 
               
               
                   
                   
                   
                 fibers and blades 
                 Y 
               
               
                   
                   
                   
                 brown glass 
                 N 
                 E8 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 brown glass 
                 N 
                 E9 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                 toluene 
                 pink blades and rectangular 
                 Y 
                 E10 
                 crystalline 2 
               
               
                   
                   
                   
                 plates 
               
               
                   
                   
                   
                 colorless blades and 
                 Y 
                 E11 
                 crystalline 2 
               
               
                   
                   
                   
                 rectangular plates 
                   
                   
                 minus peaks 
               
               
                   
                   
                   
                 colorless irregular plates 
                 Y 
                 E12 
                 crystalline 2 
               
               
                 sulfuric 
                 MeOH 
                 ACN 
                 caramel-colored, 
                 Y 
                 F1 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 off-white, morphology 
                 N 
                 F2 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 caramel-colored, 
                 Y 
                 F3 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                 EtOAc 
                 off-white, morphology 
                 Y 
                 F4 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 minus peaks 
               
               
                   
                   
                   
                 colorless, morphology 
                 Y 
                 F5 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 minus peaks 
               
               
                   
                   
                   
                 colorless, morphology 
                 Y 
                 F6 
                 crystalline 2 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 minus peaks 
               
               
                   
                   
                 IPA 
                 brown, morphology 
                 N 
                 F7 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 brown, morphology 
                 N 
                 F8 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 minus peaks 
               
               
                   
                   
                   
                 brown, morphology 
                 N 
                 F9 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 toluene 
                 off-white, morphology 
                 partial 
                 F10 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 white, morphology unknown 
                 N 
                 F11 
                 crystalline 1 
               
               
                   
                   
                   
                 white, morphology unknown 
                 N 
                 F12 
                 crystalline 1 
               
               
                 phosphoric 
                 MeOH 
                 ACN 
                 orange, morphology 
                 N 
                 G1 
                 crystalline 2 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 orange, morphology 
                 N 
                 G2 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 orange, morphology 
                 N 
                 G3 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                 EtOAc 
                 off-white, morphology 
                 N 
                 G4 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 off-white, morphology 
                 N 
                 G5 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 off-white, morphology 
                 N 
                 G6 
                 crystalline 1 + 
               
               
                   
                   
                   
                 unknown 
                   
                   
                 peaks 
               
               
                   
                   
                   
                 blades 
                 Y 
               
               
                   
                   
                 IPA 
                 brown, morphology 
                 N 
                 G7 
                 crystalline 3 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 caramel-colored, 
                 N 
                 G8 
                 crystalline 4 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 pink, morphology unknown 
                 N 
                 G9 
                 amorphous 
               
               
                   
                   
                   
                   
                   
                   
                 with peaks 
               
               
                   
                   
                 toluene 
                 off-white, morphology 
                 N 
                 G10 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 white, morphology unknown 
                 N 
                 G11 
                 crystalline 1 
               
               
                   
                   
                   
                 white, morphology unknown 
                 N 
                 G12 
                 crystalline 1 
               
               
                 none 
                 MeOH 
                 ACN 
                 yellow glass 
                 N 
                 H1 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 yellow glass 
                 N 
                 H2 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                 EtOAc 
                 colorless, morphology 
                 N 
                 H4 
                 amorphous 
               
               
                   
                   
                   
                 unknown 
               
               
                   
                   
                   
                 fibers 
                 Y 
               
               
                   
                   
                   
                 colorless fibers 
                 Y 
                 H5 
                 amorphous 
               
               
                   
                   
                 IPA 
                 yellow fibers and 
                 Y 
                 H7 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
                   
                   
                 yellow glass 
                 N 
                 H8 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 yellow oil 
                 N 
                 H9 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                 toluene 
                 yellow glass 
                 N 
                 H10 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
                 Y 
               
               
                   
                   
                   
                 colorless oil and 
                 N 
                 H11 
                 amorphous 
               
               
                   
                   
                   
                 morphology unknown 
               
               
                   
               
               
                   a MeOH = methanol. 
               
               
                   b ACN = acetonitrile, EtOAc = ethyl acetate, IPA = isopropanol. 
               
               
                   c B = birefringence, E = extinction; samples observed under microscope with crossed polarized light; Y = yes, N = no. 
               
            
           
         
       
     
     Summary of Crystalline Salts from Wellplates: Salt MicroScreen™ 
     The following new crystalline salts were discovered from wellplate crystallization experiments: 
     acetate, 
     adipate, 
     citrate, 
     gentisate, 
     glutarate, 
     glycolate, 
     hydrobromide, 
     lactate, 
     L-malate, 
     maleate, 
     phosphate, 
     succinate, 
     sulfate. 
     The crystalline salts are summarized in Table 18A above. The preparation and crystallization experiments are discussed below. 
     Acetate Salt 
     A new crystalline XRPD pattern (crystalline 1) was observed in the experiments with acetic acid in acetone and methanol ( FIG. 21 ). Material exhibiting this XRPD pattern was also produced in the microplate recrystallization experiments using methanol:acetonitrile 1:1 and methanol: ethyl acetate 1:1 (see summary table). 
     The acetate salt (crystalline 1) was initially prepared on approximately 50-mg scale from methanol solution (evaporation to dryness, Table 22A). The salt structure was confirmed by proton NMR ( FIG. 22 , Table 23A). Approximate solubility data for the acetate salt are given in Table 61A. 
     The acetate salt (crystalline 1) was crystallized with approximately 70% yield by fast evaporation from methanol (Table 24A). The material was characterized using thermal techniques ( FIG. 23 , Table 25A). A two-step weight loss of approximately 16% was observed in TG at higher temperatures and was likely due to salt decomposition with the loss of the acetic acid. An endotherm at approximately 190° C. with a shoulder at 194° C. in DSC corresponded to the weight loss in TG. Thus, the shoulder at 194° C. probably indicated the melt of the free base. Therefore, the acetate salt decomposed on heating to higher temperatures (approximately 100-150° C.). 
     The aqueous solubility of the acetate salt was approximately 14 mg/mL (Table 64A). 
     
       
         
           
               
             
               
                 TABLE 22A 
               
               
                   
               
               
                 Salt Preparation Attempts from Compound 2 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Solvent 
                   
                   
                 XRPD 
               
               
                 Acid a   
                 System 
                 Conditions b   
                 Description c   
                 Result d   
               
               
                   
               
               
                 acetic 
                 MeOH 
                 FE 
                 translucent glassy film, not 
                 crystalline 1 
               
               
                   
                   
                   
                 birefringent; white, 
               
               
                   
                   
                   
                 morphology unknown, 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                 acetone 
                 FE 
                 brownish glassy solid, not 
                 — 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                   
                 SE 
                 brownish glassy solid, not 
                 — 
               
               
                   
                   
                   
                 birefringent 
               
               
                 adipic 
                 MeOH 
                 FE 
                 white needles, birefringent; 
                 crystalline 1 
               
               
                   
                   
                   
                 white, morphology unknown, 
               
               
                   
                   
                   
                 not birefringent 
               
               
                   
                 acetone:MeOH 
                 FE 
                 yellow glassy solid, not 
                 — 
               
               
                   
                 95:5 
                   
                 birefringent 
               
               
                   
                   
                 SE 
                 brownish glassy solid, not 
                 — 
               
               
                   
                   
                   
                 birefringent 
               
               
                 citric 
                 MeOH 
                 FE 
                 white flakes, partially 
                 crystalline 1 
               
               
                   
                   
                   
                 birefringent; clear oily film, 
               
               
                   
                   
                   
                 not birefringent 
               
               
                   
                 acetone:MeOH 
                 FE 
                 clear glassy solid, not 
                 — 
               
               
                   
                 96:4 
                   
                 birefringent 
               
               
                   
                   
                 SE 
                 off-white spherulites of tiny 
                 crystalline 2 
               
               
                   
                   
                   
                 needles 
               
               
                 gentisic 
                 MeOH 
                 RT slurry, 4d e   
                 clear solution 
                 — 
               
               
                   
                   
                 CP w/ ether, RT 
                 off-white wispy chunks 
                 IS 
               
               
                   
                   
                 3d f   
                 (visual) 
               
               
                   
                 MeOH:EtOAc 
                 FE 
                 clear oily film, not 
                 crystalline 1 
               
               
                   
                 1:1 
                   
                 birefringent; white, 
               
               
                   
                   
                   
                 morphology unknown, 
               
               
                   
                   
                   
                 birefringent 
               
               
                 glutaric 
                 MeOH:EtOAc 
                 FE 
                 white dendridic fibers and 
                 crystalline 1 
               
               
                   
                 1:1 
                   
                 morphology unknown, 
               
               
                   
                   
                   
                 birefringent 
               
               
                 glycolic 
                 MeOH:ACN 
                 FE 
                 white, morphology unknown, 
                 crystalline 1 
               
               
                   
                 1:1 
                   
                 partially birefringent 
               
               
                   
               
            
           
           
               
            
               
                   a Acid/API molar ratio is 1:1 unless specified otherwise 
               
               
                   b CP = crash precipitation, FE = fast evaporation, SE = slow evaporation, RT = ambient 
               
               
                 temperature, d = days; reported times are approximate 
               
               
                   c Samples observed under microscope with crossed polarized light 
               
               
                   d IS = insufficient solids for analysis 
               
               
                   e Precipitate generated upon acid addition 
               
               
                   f Opaque liquid generated upon antisolvent addition 
               
               
                   g 1:1 equivalents Acid/API 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Solvent 
                   
                   
                 XRPD 
               
               
                 Acid a   
                 System 
                 Conditions b   
                 Description c   
                 Result d   
               
               
                   
               
               
                 HBr 
                 acetone 
                 FE 
                 off-white needles, blades, and 
                 crystalline 3 
               
               
                   
                   
                   
                 morphology unknown, 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                 MEK 
                 FE 
                 clear fibers, birefringent; 
                 — 
               
               
                   
                   
                   
                 purple sticky film, not 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                   
                   
                 clear, morphology unknown, 
                 — 
               
               
                   
                   
                   
                 birefringent; purple sticky 
               
               
                   
                   
                   
                 film, not birefringent 
               
               
                   
                 TFE 
                 spontaneous 
                 white, morphology unknown, 
                 crystalline 1 
               
               
                   
                   
                 precipitation 
                 not birefringent 
               
               
                 lactic 
                 MeOH:toluene 
                 FE 
                 clear glassy film, not 
                 amorphous 
               
               
                   
                 1:1 
                   
                 birefringent; colorless fibers, 
               
               
                   
                   
                   
                 birefringent 
               
               
                 maleic 
                 MeOH 
                 FE 
                 white, morphology unknown, 
                 crystalline 1 + 
               
               
                   
                   
                   
                 birefringent 
                 peaks 
               
               
                   
                 acetone:MeOH 
                 FE 
                 white, morphology unknown, 
                 crystalline 1 + 
               
               
                   
                 96:4 
                   
                 birefringent and yellowish 
                 peaks 
               
               
                   
                   
                   
                 film, not birefringent 
               
               
                 L-malic 
                 MeOH 
                 RT slurry, 4d f   
                 clear solution 
                 — 
               
               
                   
                   
                 CP w/ ether, RT 
                 dark, wispy solids, not 
                 amorphous 
               
               
                   
                   
                 3d e   
                 birefringent 
               
               
                   
                   
                 FE 
                 white, morphology unknown, 
                 crystalline 1 
               
               
                   
                   
                   
                 birefringent 
               
               
                 phosphoric 
                 MeOH 
                 RT stir 3d f   
                 dark wispy solids, irregular 
                 crystalline 6 
               
               
                   
                   
                   
                 particles, birefringent 
               
               
                   
                 TFE/MeOH 
                 RT stir 3d f   
                 dark wispy solids, irregular 
                 low crystalline 7 
               
               
                   
                   
                   
                 particles, birefringent 
               
               
                   
                 acetone 
                 FE 
                 white flakes, birefringent 
                 amorphous 
               
               
                   
                 MeOH 
                 FE 
                 white, morphology unknown, 
                 crystalline 5 
               
               
                   
                   
                   
                 partially birefringent 
               
               
                   
               
            
           
           
               
            
               
                   a Acid/API molar ratio is 1:1 unless specified otherwise 
               
               
                   b CP = crash precipitation, FE = fast evaporation, SE = slow evaporation, RT = ambient 
               
               
                 temperature, d = days; reported times are approximate 
               
               
                   c Samples observed under microscope with crossed polarized light 
               
               
                   d IS = insufficient solids for analysis 
               
               
                   e Opaque liquid generated upon antisolvent addition 
               
               
                   f Precipitate generated upon acid addition 
               
               
                   g 1:1 equivalents Acid/API 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Solvent 
                   
                   
                 XRPD 
               
               
                 Acid a   
                 System 
                 Conditions b   
                 Description c   
                 Result d   
               
               
                   
               
               
                 phosphoric 
                 MEK 
                 FE 
                 clear fibers, birefringent; 
                 — 
               
               
                   
                   
                   
                 light brown sticky film, not 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                   
                   
                 purple sticky film, not 
                 — 
               
               
                   
                   
                   
                 birefringent 
               
               
                 succinic 
                 MeOH 
                 FE 
                 white, morphology unknown, 
                 crystalline 1 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                 TFE:MeOH 
                 FE 
                 clear, glassy, not birefringent 
                 — 
               
               
                   
                 5:1 
               
               
                   
                 TFE:MeOH 
                 FE 
                 white, morphology unknown, 
                 crystalline 3 
               
               
                   
                 10:1 
                   
                 birefringent 
               
               
                   
                   
                 SE 
                 off-white, morphology 
                 crystalline 1 
               
               
                   
                   
                   
                 unknown, birefringent 
               
               
                   
                 toluene:MeOH 
                 FE 
                 white, morphology unknown, 
                 crystalline 1 
               
               
                   
                 1:1 
                   
                 partially birefringent 
               
               
                 sulfuric 
                 MeOH:EtOAc 
                 FE 
                 off-white needles, 
                 crystalline 6 
               
               
                   
                 1:1 
                   
                 birefringent 
               
               
                   
                 acetone 
                 API/Acid (2/1); FE 
                 white, glassy, not birefringent 
                 amorphous 
               
               
                   
                 MeOH 
                 API/Acid (2/1); FE 
                 white, small needles, 
                 crystalline 1 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                 acetone 
                 API/Acid (2/1); 
                 off-white, clump of irregular 
                 crystalline 7 
               
               
                   
                   
                 slurry 
                 shaped particles, birefringent 
               
               
                   
                 acetone 
                 API/Acid (1/1); FE 
                 white, irregular shape, 
                 crystalline 5 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                 MeOH 
                 API/Acid (1/1); FE 
                 white, fragments, birefringent 
                 crystalline 6 
               
               
                   
                 MeOH 
                 API/Acid (1/1); SE 
                 white, fragments, birefringent 
                 crystalline 6 
               
               
                   
                 acetone/MeOH 
                 RT stir 1d/SE 
                 wisps, irregular particles, 
                 crystalline 1 
               
               
                   
                   
                 (RT stir 4d total) e   
                 blades, birefringent 
                 (small amount 
               
               
                   
                   
                   
                   
                 of sample) 
               
               
                   
                 TFE/MeOH 
                 RT stir 3d e   
                 dark fine wisps, not 
                 low crystalline 8 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
               
            
           
           
               
            
               
                   a Acid/API molar ratio is 1:1 unless specified otherwise 
               
               
                   b CP = crash precipitation, FE = fast evaporation, SE = slow evaporation, RT = ambient 
               
               
                 temperature, d = days; reported times are approximate 
               
               
                   c Samples observed under microscope with crossed polarized light 
               
               
                   d IS = insufficient solids for analysis 
               
               
                   e Precipitate generated upon acid addition 
               
               
                   f 1:1 equivalents Acid/API 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 23A 
               
             
            
               
                   
               
               
                 Characterization of Acetate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 24A 
               
             
            
               
                   
               
               
                 Salt Preparation Scale-up Experiments using compound 2 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Solvent/Solvent 
                   
                   
                 Yield 
                 XRPD 
               
               
                 Acid 
                 System 
                 Method a   
                 Description 
                 (%) 
                 Result d   
               
               
                   
               
               
                 acetic 
                 MeOH 
                 SC 
                 clear solution 
                 — 
                 — 
               
               
                   
                 MeOH 
                 FE 
                 off-white solid, 
                 70.2 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown, 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                 acetonitrile:MeOH 
                 FE 
                 yellow, dendridic 
                 74.4 
                 crystalline 1 
               
               
                   
                 1:1 
                   
                 formations, 
               
               
                   
                   
                   
                 birefringent 
               
               
                 adipic 
                 MeOH 
                 SC 
                 clear solution 
                 — 
                 — 
               
               
                   
                 MeOH 
                 FE 
                 off-white solid, 
                 72.4 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown, 
               
               
                   
                   
                   
                 birefringent 
               
               
                   
                 acetonitrile:MeOH 
                 FE 
                 light yellow, 
                 58.1 
                 crystalline 1 
               
               
                   
                 1:1 
                   
                 spherulites of blades, 
               
               
                   
                   
                   
                 birefringent 
               
               
                 citric 
                 acetone:MeOH 
                 SC 
                 off-white, spherulites 
                 109.6 b   
                 crystalline 2 
               
               
                   
                 98:2 
                   
                 of needles, 
               
               
                   
                   
                   
                 birefringent 
               
               
                 glycolic 
                 acetonitrile:MeOH 
                 SC 
                 white, blades, 
                 80.5 
                 crystalline 1 
               
               
                   
                 1:1 
                   
                 birefringent 
               
               
                 HBr 
                 acetonitrile:MeOH 
                 SC 
                 clear solution 
                 — 
                 — 
               
               
                   
                 1:1 
               
               
                   
                 acetonitrile:MeOH 
                 SC, then 
                 yellowish solid, 
                 63.7 
                 crystalline 1 
               
               
                   
                 1:1 
                 FE 
                 morphology unknown, 
               
               
                   
                   
                   
                 partially birefringent 
               
               
                   
                   
                   
                 yellow solid, 
                 47.6 
                 crystalline 1 
               
               
                   
                   
                   
                 morphology unknown, 
               
               
                   
                   
                   
                 not birefringent 
               
               
                 phosphoric 
                 MeOH 
                 precipitation 
                 white solid 
                 89.4 
                 crystalline 2 
               
               
                   
                   
                 at 
               
               
                   
                   
                 55° C. 
               
               
                   
                 MeOH 
                 FE 
                 white solid, 
                 82 
                 crystalline 8, 
               
               
                   
                   
                   
                 morphology unknown, 
                   
                 (crystalline 5 
               
               
                   
                   
                   
                 not birefringent 
                   
                 is crystalline 
               
               
                   
                   
                   
                   
                   
                 8 + peaks) 
               
               
                   
                 MeOH 
                 FE 
                 white, morphology 
                 88.2 
                 crystalline 8 
               
               
                   
                   
                   
                 unknown, birefringent 
               
               
                   
                   
                   
                 and off-white solid, 
               
               
                   
                   
                   
                 rosettes from irregular 
               
               
                   
                   
                   
                 crystals, birefringent 
               
               
                   
               
               
                   a FE = fast evaporation, SC = slow cool 
               
               
                   b possible dihydrate, acetone solvate, or mixed hydrate/solvate obtained 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 25A 
               
             
            
               
                   
               
               
                 Characterization of Acetate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                 DSC a   
                 endo 190, 194 (shoulder) 
               
               
                   
                 TGA b   
                 9.88 @ 15-160 
               
               
                   
                   
                 6.37 @160-195 
               
               
                   
                   
               
               
                   
                   a endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   b weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Adipate 
     A new crystalline XRPD pattern and a similar low crystalline pattern (crystalline 1 and low crystalline 1) were observed in the experiments with adipic acid in acetone. Material exhibiting the XRPD pattern of crystalline 1 without some peaks was produced from methanol ( FIGS. 24   a  to  d ). 
     Material exhibiting the XRPD pattern of crystalline 1 also resulted from the microplate recrystallization experiment using methanol:acetonitrile 1:1 and methanol: ethyl acetate 1:1 (see summary table). 
     The adipate salt (crystalline 1) was prepared on approximately 50-mg scale by fast evaporation in methanol (to dryness, Table 22A above). The salt structure was confirmed by proton NMR ( FIG. 25 , Table 26A). Approximate solubility data for the adipate salt are given in Table 62A. 
     The adipate salt (crystalline 1) was crystallized by fast evaporation in methanol (approx. 72% yield) and acetonitrile:methanol 1:1 (approx. 58% yield) (Table 24A above). The sample prepared from methanol was analyzed by thermal techniques ( FIG. 26 , Table 27A). The sample exhibited a gradual weight loss of approximately 5.0% from 20 to 155° C. in TG. A smaller broad endotherm (likely desolvation/dehydration) at approximately 91° C. in DSC was followed by a broad intense endotherm at approximately 145° C. The DSC data likely indicated melt/decomposition occurred simultaneously. 
     The aqueous solubility of the adipate salt was approximately 10 mg/mL (Table 64A). 
     
       
         
           
               
             
               
                 TABLE 26A 
               
             
            
               
                   
               
               
                 Characterization of Adipate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 27A 
               
             
            
               
                   
               
               
                 Characterization of Adipate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                 DSC a   
                 endo 91(small), 145 
               
               
                   
                 TGA b   
                 5.00 @ 20-155 
               
               
                   
                   
               
               
                   
                 a and b as above 
               
            
           
         
       
     
     Citrate 
     A new crystalline XRPD pattern (crystalline 1) was observed in the experiment with citric acid in acetone. A similar low crystalline XPRD pattern (low crystalline 1) was observed in the experiments utilizing acetone, methanol, and methyl ethyl ketone as solvents ( FIG. 27   a  to  d ). 
     Material exhibiting the XRPD pattern of crystalline 1 also resulted from a microplate recrystallization experiment using methanol:acetonitrile 1:1 and methanol: ethyl acetate 1:1 (see summary table). 
     Two crystalline forms of the citrate salt were prepared from scale-up experiments (Table 22A). Material exhibiting the XRPD pattern of crystalline 1 resulted from a fast evaporation experiment in methanol. A new material with an XRPD pattern designated as crystalline 2 was produced in a slow evaporation experiment in acetone:methanol 96:4 (Table 22A). The salt structure was confirmed by proton NMR for both samples ( FIG. 29 ,  FIG. 30 , Table 28A, Table 29A). Based on NMR, impurities were present in the crystalline 2 material. 
     The citrate salt (crystalline 2) was scaled up by crystallization in acetone:methanol 98:2 (slow cool, Table 24A). Approximately 110% yield was calculated, however, an insignificant weight loss (0.3%) was observed after the material had been dried in vacuum for three days. Based on proton NMR, approximately 0.5 moles of acetone were found per one mole of the compound ( FIG. 35 ). 
     The citrate salt was characterized by thermal techniques ( FIG. 31 , Table 30A). A weight loss of approximately 1% between 25 and 115° C. in TG was probably due to desolvation. A broad endotherm was observed in DSC at approximately 82° C., likely due to loss of solvent. The DSC exhibited a sharper intensive endotherm at approximately 148° C. Based on weight loss in TG, the endotherm likely resulted from simultaneous melt/decomposition. 
     The aqueous solubility of the citrate salt was approximately 12 mg/mL (Table 64A). 
     
       
         
           
               
             
               
                 TABLE 28A 
               
             
            
               
                   
               
               
                 Characterization of Citrate Salt, crystalline 1 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 29A 
               
             
            
               
                   
               
               
                 Characterization of Citrate Salt, crystalline 2 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 2 
               
               
                   
                   1 H NMR 
                 impurities present 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 30A 
               
             
            
               
                   
               
               
                 Characterization of Citrate Salt, crystalline 2 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 2 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                 DSC a   
                 endo 82 (small), 148 
               
               
                   
                 TGA b   
                 1.01 @ 25-115 
               
               
                   
                   
               
               
                   
                   a endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   b weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Gentisate 
     No crystalline materials were generated in the experiments with gentisic acid in the original wellplate salt preparation (Table 17A). 
     Two crystalline materials exhibiting XRPD patterns designated as crystalline 1 and crystalline 2 resulted from wellplate recrystallization experiments in methanol: ethyl acetate 1:1 ( FIGS. 32   a ,  32   b  and  32   c , Table 20A). Based on proton NMR, the crystalline 2 material was the gentisate salt that contained approximately 0.7 moles of ethyl acetate ( FIG. 34 , Table 32A). 
     The crystalline 1 material was obtained in a scale-up attempt by fast evaporation in methanol: ethyl acetate 1:1 (evaporation to dryness,). Based on  1 H NMR, the material was a likely mixture of the free base and the gentisate salt ( FIG. 33 , Table 31A). 
     The aqueous solubility of the gentisate salt was lower than 1 mg/mL (Table 63A) 
     
       
         
           
               
             
               
                 TABLE 31A 
               
             
            
               
                   
               
               
                 Characterization of Gentisate Salt, crystalline 1 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 salt + free base 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 32A 
               
             
            
               
                   
               
               
                 Characterization of Gentisate Salt, crystalline 2 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 2 
               
               
                   
                   1 H NMR 
                 0.7 mole of EtOAc per 1 mole of 
               
               
                   
                   
                 compound 
               
               
                   
                   
               
            
           
         
       
     
     Glutarate 
     No crystalline materials were generated in the experiments with glutaric acid in the original wellplate salt preparation (Table 17A). 
     Material exhibiting an XRPD pattern designated as crystalline 1 was generated in the microplate recrystallization experiments using methanol:acetonitrile 1:1 and methanol: ethyl acetate 1:1 ( FIGS. 35   a ,  35   b  and  35   c , Table 20A). 
     The glutarate salt (crystalline 1) was crystallized by fast evaporation in methanol: ethyl acetate 1:1 (evaporation to dryness, Table 22A). The salt structure was confirmed by  1 H NMR ( FIG. 36 , Table 33A). 
     The aqueous solubility of the glutarate salt was approximately 3 mg/mL (Table 63A). 
     
       
         
           
               
             
               
                 TABLE 33A 
               
             
            
               
                   
               
               
                 Characterization of Glutarate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     Glycolate 
     No crystalline materials were generated in the experiments with glycolic acid in the original wellplate salt preparation (Table 17A). 
     Material exhibiting an XRPD pattern designated as crystalline 1 resulted from the microplate recrystallization experiment in methanol:acetonitrile 1:1 ( FIGS. 37   a ,  37   b  and  37   c , Table 20A). 
     The glycolate salt (crystalline 1) was produced on approx. 50-mg scale by fast evaporation using methanol:acetonitrile 1:1 (Table 22A). The salt structure was confirmed by  1 H NMR ( FIG. 38 , Table 34A, residual acetonitrile present). 
     The glycolate salt was prepared with approx. 80% yield by slow cooling in acetonitrile:methanol 1:1 (Table 24A). The material was analyzed using thermal techniques ( FIG. 39 , Table 35A). The baseline in DSC at lower temperatures indicated possible loss of residual solvent. A weight loss of approximately 8.5% in TG was accompanied by a sharp endotherm at approximately 147° C., probably due to the melt and concurrent decomposition. DSC and TG thermograms exhibited further decomposition above 150° C. (endotherms at 192 and 204° C.). 
     The aqueous solubility of the glycolate salt was approximately 27 mg/mL (Table 64A). 
     
       
         
           
               
             
               
                 TABLE 34A 
               
             
            
               
                   
               
               
                 Characterization of Glycolate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 consistent w/structure, 
               
               
                   
                   
                 residual acetonitrile 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 35A 
               
             
            
               
                   
               
               
                 Characterization of Glycolate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                 DSC 
                 endo 147 (87 J/g), 192, 204 
               
               
                   
                 TGA 
                 8.52 @ 20-155 
               
               
                   
                   
               
            
           
         
       
     
     Hydrobromide 
     The crystalline XRPD patterns of the hydrobromide salt found in the screen are presented in  FIGS. 40   a  to  40   e.    
     Two new crystalline XRPD patterns were observed in the wellplate preparation experiments with hydrobromic acid in trifluoroethanol (crystalline 1) and in acetone and methyl ethyl ketone (crystalline 2) (Table 19A). 
     Material exhibiting the XRPD pattern of crystalline 1 was also produced in wellplate recrystallization experiments using methanol: ethyl acetate, methanol: isopropanol, and methanol:toluene 1:1 solvent systems (Table 21A). 
     Material exhibiting the XRPD pattern of crystalline 2 was obtained in wellplate recrystallization experiments using methanol: acetonitrile and methanol:isopropanol 1:1 (Table 21A). Presence of impurities was noted in proton NMR ( FIG. 42 , Table 37A). A low crystalline pattern 2 was detected by XRPD in a recrystallization experiment in methanol:acetonitrile 1:1. 
     Two crystalline forms of the HBr salt were prepared from the scale-up experiments (Table 22A). Material exhibiting the XRPD pattern of crystalline 1 resulted from a fast evaporation experiment in 2,2,2-trifluoroethanol (TFE) and contained residual trifluoroethanol, based on  1 H NMR ( FIG. 41 , Table 36A). Material exhibiting a new XRPD pattern designated as crystalline 3 was produced by fast evaporation in acetone. It contained impurities as shown by proton NMR ( FIG. 43 , Table 38A). 
     The hydrobromide salt was crystallized from acetonitrile:methanol 1:1 with approx. 64% yield and characterized by thermal techniques (Table 24A,  FIG. 44 , Table 39A). Crystalline 1 material was produced from two preparation experiments. A weight loss of approximately 0.72% was observed in TG between 19 and 205° C. The DSC indicated initial loss of residual solvent (broad endotherm at approx. 48° C.). The endotherm at approximately 234° C. was likely due to the melt. 
     The aqueous solubility of the hydrobromide salt was approximately 16 mg/mL (Table 64A). 
     
       
         
           
               
             
               
                 TABLE 36A 
               
             
            
               
                   
               
               
                 Characterization of Hydrobromide Salt, Crystalline 1 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 consistent w/structure, 
               
               
                   
                   
                 residual trifluoroethanol 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 37A 
               
             
            
               
                   
               
               
                 Characterization of Hydrobromide Salt, Crystalline 2 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 2 
               
               
                   
                   1 H NMR 
                 impurities present 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 38A 
               
             
            
               
                   
               
               
                 Characterization of Hydrobromide Salt, Crystalline 3 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 3 
               
               
                   
                   1 H NMR 
                 impurities present 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 39A 
               
             
            
               
                   
               
               
                 Characterization of Hydrobromide Salt, Crystalline 1 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                 DSC a   
                 endo 48 (small), 198 (small), 234 (77 J/g) 
               
               
                   
                 TGA b   
                 0.72 @ 19-205 
               
               
                   
                   
               
               
                   
                   a endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   b weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Lactate 
     No crystalline materials were generated in the experiments with lactic acid in the original wellplate salt preparation (Table 19A). 
     Material exhibiting an XRPD pattern designated as crystalline 1 resulted from the microplate recrystallization experiment in methanol:toluene 1:1 ( FIG. 45 , Table 21A). A mixture of the free base and a small amount of lactic acid with impurities was detected by proton NMR (very small amount of material,  FIG. 46 , Table 40A). 
     A scale-up attempt by fast evaporation using the same solvent system was unsuccessful and resulted in amorphous material (Table 22A). 
     
       
         
           
               
             
               
                 TABLE 40A 
               
             
            
               
                   
               
               
                 Characterization of Lactate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 free base + small amount of lactic acid 
               
               
                   
                   
                 (very small concentration) 
               
               
                   
                   
               
            
           
         
       
     
     L-Malate 
     A new crystalline XRPD pattern (crystalline 1) was observed in the original wellplate salt preparation with L-malic acid in methanol ( FIGS. 47   a  and  47   b , Table 17A). Material exhibiting the XRPD pattern of crystalline 1 was also produced in a wellplate recrystallization experiment in methanol:acetonitrile 1:1 (Table 20A). 
     The L-malate salt was also prepared on approx. 50-mg scale by fast evaporation in methanol (evaporation to dryness, Table 22A). The salt structure was confirmed by proton NMR ( FIG. 48 , Table 41A). 
     The aqueous solubility of the L-malate salt was approximately 4 mg/mL (Table 63A). 
     
       
         
           
               
             
               
                 TABLE 41A 
               
             
            
               
                   
               
               
                 Characterization of L-Malate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     Maleate 
     Two new crystalline XRPD patterns were observed in the experiments with maleic acid in acetone and methanol (crystalline 1 and crystalline 1 plus one peak). Both results were obtained from both solvents. A low crystalline material with the XRPD pattern similar to crystalline 1 (low crystalline 1) resulted from trifluoroethanol ( FIGS. 49   a  to  49   d , Table 19A). 
     Two crystalline materials exhibiting the XRPD patterns of crystalline 1 and crystalline 1 plus peak were produced in the wellplate recrystallization experiments in methanol: acetonitrile and methanol: ethyl acetate 1:1 solvent systems ( FIG. 49 , Table 21A). Material exhibiting the XRPD pattern of crystalline 1 plus peak was also produced in methanol:toluene 1:1. 
     The maleate salt (crystalline 1 plus peaks) was prepared on approximately 50-mg scale by fast evaporation in methanol and acetone:methanol 96:4 (Table 22A). The salt structure was confirmed by proton NMR ( FIG. 50 , Table 42A). 
     The aqueous solubility of the maleate salt was approximately 3 mg/mL (Table 63A). 
     
       
         
           
               
             
               
                 TABLE 42A 
               
             
            
               
                   
               
               
                 Characterization of Maleate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 maleate 
               
               
                   
                   
                 (crystalline 1 + peaks) 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     Phosphate 
     Four new crystalline XRPD patterns were found in the wellplate experiments with phosphoric acid ( FIGS. 51   a  to  51   i  and  FIG. 52 , Table 19A). Material exhibiting an XRPD pattern designated as crystalline 1 was produced from methanol and trifluoroethanol. Material exhibiting an XRPD pattern designated as crystalline 1 plus peaks was produced from acetone. Material with a low crystalline 1 pattern resulted from an experiment in methanol. 
     Material exhibiting an XRPD pattern designated as crystalline 2 resulted from experiments in acetone. 
     Two crystalline materials exhibiting XRPD patterns designated as crystalline 3 and crystalline 4 were produced in experiments in methyl ethyl ketone. 
     All the four new crystalline materials were reproduced in wellplate recrystallization experiments by addition of antisolvents such as acetonitrile, ethyl acetate, toluene, and isopropanol to methanol solutions (Table 21A). Based on proton NMR, materials of crystalline 2, crystalline 3, and crystalline 4 had impurities ( FIG. 53 ,  FIG. 54 ,  FIG. 55  and Table 44A, Table 45A, Table 46A). 
     The phosphate salt exhibiting a new XRPD pattern of crystalline 5 (also called crystal modification X) was produced in a scale-up experiment by fast evaporation to dryness in methanol (Table 22A). The salt structure was confirmed by proton NMR ( FIG. 56 , Table 43A). Two new XRPD patterns for the phosphate salt—crystalline 6 and low crystalline 7—resulted from the scale-up slurry experiments (Table 22A). 
     Attempts to prepare additional quantities of crystalline materials 1-4 were not successful. Amorphous material resulted from fast evaporation to dryness in acetone. 
     The phosphate salt (crystalline 2) was crystallized with approx. 89% yield by precipitation from methanol at approx. 55° C. (Table 24A). 
     The phosphate salt exhibiting a new XRPD pattern designated as crystalline 8 was prepared with approx. 82% yield by fast evaporation from methanol (Table 24A). Crystalline 8 is probably a more thermodynamically stable form of the phosphate salt. After comparison of the XRPD data, crystalline pattern 5 appeared to be very similar to crystalline pattern 8 with some peaks ( FIG. 52 ). 
     The phosphate salt, crystalline 8, was reproduced in the second scale-up experiment using the same crystallization conditions (Table 24A). The material was analyzed using proton NMR and thermal techniques ( FIG. 57 ,  FIG. 58 , Table 47A). The TG data showed an insignificant weight loss of approximately 0.24% from 18 to 200° C. A single endotherm in DSC at approximately 233° C. probably corresponded to the melt and initial decomposition. 
     The aqueous solubility of the phosphate salt was approximately 2-3 mg/mL (Table 64A). 
     
       
         
           
               
             
               
                 TABLE 43A 
               
             
            
               
                   
               
               
                 Characterization of Phosphate Salt, 
               
               
                 Crystalline 5 (Crystalline 8 + peaks) 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 5 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 44A 
               
             
            
               
                   
               
               
                 Characterization of Phosphate Salt, Crystalline 2 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 2 
               
               
                   
                   1 H NMR 
                 impurities present 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 45A 
               
             
            
               
                   
               
               
                 Characterization of Phosphate Salt, Crystalline 3 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 3 
               
               
                   
                   1 H NMR 
                 impurities present 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 46A 
               
             
            
               
                   
               
               
                 Characterization of Phosphate Salt, Crystalline 4 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 4 
               
               
                   
                   1 H NMR 
                 impurities present 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 47A 
               
             
            
               
                   
               
               
                 Characterization of Phosphate Salt, Crystalline 8 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 8 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                 DSC a   
                 endo 233 (134 J/g) 
               
               
                   
                 TGA b   
                 0.24 @ 18-200 
               
               
                   
                   
               
               
                   
                   a endo = endotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   b weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
            
           
         
       
     
     Succinate 
     Material exhibiting an XRPD pattern designated as crystalline 1 was observed in the experiments with succinic acid in acetone, methanol, and trifluoroethanol ( FIG. 60 , Table 19A). Experiments utilizing acetone and trifluoroethanol also produced low crystalline 1 material. 
     Material exhibiting the XRPD pattern of crystalline 1 was then produced in recrystallization experiments using methanol: acetonitrile and methanol: ethyl acetate 1:1 (Table 21A). 
     Two new crystalline materials exhibiting XRPD patterns designated as crystalline 2 and crystalline 2 minus peaks were generated in recrystallization experiments in methanol:toluene 1:1 (Table 21A). Based on  1 H NMR, impurities were present in the succinate salt of crystalline 2 ( FIG. 61 , Table 49A). 
     Two crystalline forms of the succinate salt were prepared from the scale-up experiments (Table 22A). Material exhibiting the XRPD pattern of crystalline 1 resulted from the following experiments: fast evaporation in methanol, fast evaporation in toluene:methanol 1:1, and slow evaporation in methanol: TFE 1:10. The structure of the succinate salt produced from methanol was confirmed by  1 H NMR ( FIG. 60 , Table 49A). 
     A new material with an XRPD pattern designated as crystalline 3 was produced from a fast evaporation experiment in methanol: TFE 1:10. Based on proton NMR, the succinate salt of crystalline 3 had residual amounts of trifluoroethanol ( FIG. 62 , Table 50A). 
     The aqueous solubility of the succinate salt was approximately 7-8 mg/mL (Table 63A). 
     
       
         
           
               
             
               
                 TABLE 48A 
               
             
            
               
                   
               
               
                 Characterization of Succinate Salt, Crystalline 1 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 1 
               
               
                   
                   1 H NMR 
                 consistent w/structure 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 49A 
               
             
            
               
                   
               
               
                 Characterization of Succinate Salt, Crystalline 2 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 2 
               
               
                   
                   1 H NMR 
                 impurities present 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 50A 
               
             
            
               
                   
               
               
                 Characterization of Succinate Salt, Crystalline 3 
               
            
           
           
               
               
            
               
                 Technique 
                 Analysis/Result 
               
               
                   
               
               
                 XRPD 
                 crystalline 3 
               
               
                   1 H NMR 
                 0.38 mole of TFE per 1 mole of compound (residual TFE) 
               
               
                   
               
            
           
         
       
     
     Sulfate 
     Four new crystalline XRPD patterns were observed in the wellplate experiments with sulfuric acid ( FIGS. 63   a  to  63   l , Table 19A, Table 21A):
         crystalline 1 was produced in experiments in acetone, methyl ethyl ketone, and trifluoroethanol. It was also observed in crystallization experiments using methanol solutions with acetonitrile, isopropanol, and toluene as antisolvents. Low crystalline 1 material resulted from experiments utilizing methanol and methyl ethyl ketone as solvents. Material exhibiting an XRPD pattern designated as crystalline 1 minus peaks was produced in experiments in methanol: ethyl acetate and methanol:isopropanol 1:1;   crystalline 2 was produced in an experiment in methanol; crystalline 2 minus peaks was produced in a recrystallization experiment using methanol: ethyl acetate 1:1;   crystalline 3 was produced in an experiment in acetone;   crystalline 4 was produced in an experiment in methanol.       

     Five crystalline forms of the sulfate salt were prepared from the scale-up experiments (Table 22A). Material exhibiting the XRPD pattern of crystalline 1 resulted from a fast evaporation experiment in methanol. Two equivalents of the free base were utilized in the salt preparation. The structure of the sulfate salt was confirmed by proton NMR ( FIG. 64 ). 
     The sulfate salt (crystalline 1) was characterized using thermal techniques ( FIG. 65 ). Two weight losses were observed in TG: an immediate weight loss of approximately 1.7% from 25 to 50° C. followed by a weight loss of approximately 1.5% from 50 to 150° C. The DSC thermogram exhibited two endotherms at 115 and 215° C. The first endotherm was broader than what is typically attributed to the melt and probably resulted from a simultaneous melt and dehydration. The second endotherm overlapping with an exotherm at approximately 223° C. probably corresponded to decomposition. 
     Materials with crystalline patterns 2-4 observed earlier in the wellplate preparations were not reproduced. Material of crystalline 2 minus peaks was determined to be the hydrosulfate salt by proton NMR (one equivalent of sulfuric acid used  FIG. 66 , Table 52A). Impurities were present in the material. 
     Materials exhibiting new XRPD patterns designated as crystalline 5, 6, 7, and low crystalline 8 were prepared from the scale-up experiments as summarized in  FIGS. 63   i  to  63   l  and Table 22A. The following salts were analyzed by  1 H NMR:
         crystalline 5, hydrosulfate (one equivalent of free base used,  FIG. 67 , Table 53A);   crystalline 6, sulfate (one equivalent of free base used,  FIG. 68 , Table 54A);   crystalline 7, sulfate (two equivalents of free base used,  FIG. 69 , Table 55A).       

     The aqueous solubility of the sulfate salt was lower than 1 mg/mL, and the hydrosulfate salt approximately 1 mg/mL (Table 63A). 
     
       
         
           
               
             
               
                 TABLE 51A 
               
             
            
               
                   
               
               
                 Characterization of Sulfate Salt, Crystalline 1 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 Form A (crystalline 1) 
               
               
                   
                   1 H NMR 
                 sulfate (2:1 API:acid c ) 
               
               
                   
                 DSC a   
                 endo 115 (broad), 215, exo 223 
               
               
                   
                 TGA b   
                 1.68 @ 25-50 
               
               
                   
                   
                 1.54 @ 50-150 
               
               
                   
                   
               
               
                   
                   a endo = endotherm, exo = exotherm, temperatures (C.°) reported are transition maxima. Temperatures are rounded to the nearest degree. 
               
               
                   
                   b weight loss (%) at a certain temperature; weight changes (%) are rounded to 2 decimal places; temperatures are rounded to the nearest degree 
               
               
                   
                   c actual ratio used to make the salt 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 52A 
               
             
            
               
                   
               
               
                 Characterization of Hydrosulfate Salt, Crystalline 2 minus peaks 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 2 minus peaks 
               
               
                   
                   1 H NMR 
                 hydrosulfate, impurities present 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 53A 
               
             
            
               
                   
               
               
                 Characterization of Hydrosulfate Salt, Crystalline 5 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 5 
               
               
                   
                   1 H NMR 
                 hydrosulfate (1:1 API:acid a ) 
               
               
                   
                   
               
               
                   
                   a actual ratio used to make the salt 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 54A 
               
             
            
               
                   
               
               
                 Characterization of Sulfate Salt, Crystalline 6 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 6 
               
               
                   
                   1 H NMR 
                 sulfate (1:1 API:acid a ) 
               
               
                   
                   
               
               
                   
                   a actual ratio used to make the salt 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 55A 
               
             
            
               
                   
               
               
                 Characterization of Sulfate Salt, Crystalline 7 
               
            
           
           
               
               
               
            
               
                   
                 Technique 
                 Analysis/Result 
               
               
                   
                   
               
               
                   
                 XRPD 
                 crystalline 7 
               
               
                   
                   1 H NMR 
                 sulfate (2:1 APL:acid a ) 
               
               
                   
                   
               
               
                   
                   a actual ratio used to make the salt 
               
            
           
         
       
     
     Solubility of the Salts 
     (1R)-10-Camphorsulfonate Salt 
     Approximate solubilities of (1R)-10-camphorsulfonate (camsylate) salt were determined in solvents listed in Table 56A. The (1R)-10-camphorsulfonate salt showed low solubilities in methanol and 2,2,2-trifluoroethanol (approx. 3 mg/mL) and was practically insoluble in other organic solvents and water. 
     Fumarate Salt 
     Approximate solubilities of the fumarate salt were determined in solvents listed in Table 57A. The fumarate salt was poorly soluble in water (approx. 1.4 mg/mL) and insoluble in organic solvents. 
     Malonate Salt 
     Approximate solubilities of the malonate salt were determined in solvents listed in Table 58A. The malonate salt showed low solubilities in methanol, water, acetone, and 2,2,2-trifluoroethanol and no solubility in other organic solvents. 
     L-Tartrate Salt 
     Approximate solubilities of the L-tartrate salt were determined in solvents listed in Table 59A. The L-tartrate salt showed low solubilities in methanol (approx. 8 mg/mL), acetone and water (approx. 1 mg/mL) and no solubility in other organic solvents. 
     Tosylate Salt 
     Approximate solubilities of the tosylate salt were determined in solvents listed in Table 60A. 
     Other Salts 
     Aqueous solubilities of the crystalline salts from the wellplates or scale-up preparations were estimated (Table 63A). 
     
       
         
           
               
             
               
                 TABLE 56A 
               
             
            
               
                   
               
               
                 Approximate solubilities of (1R)-10-Camphorsulfonate salt 
               
            
           
           
               
               
               
            
               
                   
                 Solvent 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 acetone 
                 &lt;2 
               
               
                   
                 acetonitrile 
                 &lt;2 
               
               
                   
                 1,4-dioxane 
                 &lt;2 
               
               
                   
                 ethanol 
                 &lt;2 
               
               
                   
                 ethyl acetate 
                 &lt;2 
               
               
                   
                 iso-propanol 
                 &lt;2 
               
               
                   
                 methanol 
                 3 
               
               
                   
                 methyl ethyl ketone 
                 &lt;2 
               
               
                   
                 tetrahydrofuran (THF) 
                 &lt;2 
               
               
                   
                 toluene 
                 &lt;2 
               
               
                   
                 2,2,2-trifluoroethanol 
                 3 
               
               
                   
                 water 
                 &lt;2 
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. Solubilities are reported to the nearest mg/mL. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 57A 
               
             
            
               
                   
               
               
                 Approximate Solubilities of Fumarate salt 
               
            
           
           
               
               
               
            
               
                   
                 Solvent 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 acetone 
                 &lt;1 
               
               
                   
                 acetonitrile 
                 &lt;1 
               
               
                   
                 1,4-dioxane 
                 &lt;1 
               
               
                   
                 ethanol 
                 &lt;1 
               
               
                   
                 ethyl acetate 
                 &lt;1 
               
               
                   
                 iso-propanol 
                 &lt;1 
               
               
                   
                 methanol 
                 &lt;1 
               
               
                   
                 methyl ethyl ketone 
                 &lt;1 
               
               
                   
                 tetrahydrofuran (THF) 
                 &lt;1 
               
               
                   
                 toluene 
                 &lt;1 
               
               
                   
                 2,2,2-trifluoroethanol 
                 &lt;1 
               
               
                   
                 water 
                 1.3 b   
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. Solubilities are reported to the nearest mg/mL. 
               
               
                   
                   b A more precise measurement of solubility was required for this solvent. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 58A 
               
             
            
               
                   
               
               
                 Approximate Solubilities of Malonate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Solvent 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 acetone 
                 1 
               
               
                   
                 acetonitrile 
                 &lt;1 
               
               
                   
                 1,4-dioxane 
                 &lt;1 
               
               
                   
                 ethanol 
                 &lt;1 
               
               
                   
                 ethyl acetate 
                 &lt;1 
               
               
                   
                 iso-propanol 
                 &lt;1 
               
               
                   
                 methanol 
                 3 
               
               
                   
                 methyl ethyl ketone 
                 &lt;1 
               
               
                   
                 tetrahydrofuran (THF) 
                 &lt;1 
               
               
                   
                 toluene 
                 &lt;1 
               
               
                   
                 2,2,2-trifluoroethanol 
                 1 
               
               
                   
                 water 
                 3 
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. Solubilities are reported to the nearest mg/mL. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 59A 
               
             
            
               
                   
               
               
                 Approximate Solubilities of L-Tartrate Salt 
               
            
           
           
               
               
               
            
               
                   
                 Solvent 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 acetone 
                 1 
               
               
                   
                 acetonitrile 
                 &lt;1 
               
               
                   
                 1,4-dioxane 
                 &lt;1 
               
               
                   
                 ethanol 
                 &lt;1 
               
               
                   
                 ethyl acetate 
                 &lt;1 
               
               
                   
                 iso-propanol 
                 &lt;1 
               
               
                   
                 methanol 
                 8 
               
               
                   
                 methyl ethyl ketone 
                 &lt;1 
               
               
                   
                 tetrahydrofuran (THF) 
                 &lt;1 
               
               
                   
                 toluene 
                 &lt;1 
               
               
                   
                 2,2,2-trifluoroethanol 
                 &lt;1 
               
               
                   
                 water 
                 1 
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. Solubilities are reported to the nearest mg/mL. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 60A 
               
             
            
               
                   
               
               
                 Approximate Solubilities of Tosylate salt 
               
            
           
           
               
               
               
            
               
                   
                 Solvent 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
               
                   
                 acetone 
                       1 b   
               
               
                   
                 acetonitrile 
                 &lt;1 
               
               
                   
                 1,4-dioxane 
                        1 c   
               
               
                   
                 ethanol 
                   5 
               
               
                   
                 ethyl acetate 
                 &lt;1 
               
               
                   
                 iso-propanol 
                 &lt;1 
               
               
                   
                 methanol 
                 19 
               
               
                   
                 methyl ethyl ketone 
                       1 b   
               
               
                   
                 tetrahydrofuran (THF) 
                 &lt;1 
               
               
                   
                 toluene 
                 &lt;1 
               
               
                   
                 2,2,2-trifluoroethanol 
                   4 
               
               
                   
                 water 
                   6 
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. Solubilities are reported to the nearest mg/mL. 
               
               
                   
                   b Dissolved after approximately 2 days. 
               
               
                   
                   c Dissolved after approximately 0.5 h. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 61A 
               
             
            
               
                   
               
               
                 Approximate Solubilities of Acetate salt 
               
            
           
           
               
               
               
            
               
                   
                 Solvent 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 acetone 
                 2 
               
               
                   
                 ethyl acetate 
                 &lt;1 
               
               
                   
                 iso-propanol 
                 1 
               
               
                   
                 methyl ethyl ketone 
                 &lt;1 
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. Solubilities are reported to the nearest mg/mL. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 62A 
               
             
            
               
                   
               
               
                 Approximate Solubilities of Adipate salt 
               
            
           
           
               
               
               
            
               
                   
                 Solvent 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 acetone 
                 3 
               
               
                   
                 ethyl acetate 
                 &lt;1 
               
               
                   
                 iso-propanol 
                 1 
               
               
                   
                 methyl ethyl ketone 
                 1 
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. Solubilities are reported to the nearest mg/mL. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 63A 
               
             
            
               
                   
               
               
                 Approximate Aqueous Solubilities of Compound 2 Salts 
               
               
                 (crude materials) 
               
            
           
           
               
               
               
            
               
                   
                 Salt 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 acetate 
                 18 
               
               
                   
                 adipate 
                 10 
               
               
                   
                 citrate-crystalline 1 
                 2 
               
               
                   
                 citrate-crystalline 2 
                 7 
               
               
                   
                 gentisate 
                 &lt;1 
               
               
                   
                 glutarate 
                 3 
               
               
                   
                 glycolate 
                 10 
               
               
                   
                 hydrobromide-crystalline 1 
                 &gt;32 
               
               
                   
                 hydrobromide-crystalline 3 
                 &gt;34 
               
               
                   
                 L-malate 
                 4 
               
               
                   
                 maleate 
                 3 
               
               
                   
                 succinate-crystalline 1 
                 8 
               
               
                   
                 succinate-crystalline 3 
                 7 
               
               
                   
                 phosphate- 
                 9 
               
               
                   
                 crystalline 5 ≡ crystalline 8 + peaks 
               
               
                   
                 sulfate-crystalline 1 
                 &lt;1 
               
               
                   
                 sulfate-crystalline 6 
                 &lt;1 
               
               
                   
                 hydrosulfate-crystalline 5 
                 1 
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. Solubilities are reported to the nearest mg/mL. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 64A 
               
             
            
               
                   
               
               
                 Approximate Aqueous Solubilities of Compound 2 Salts (scale-up 
               
               
                 crystallizations) 
               
            
           
           
               
               
               
            
               
                   
                 Salt 
                 Solubility (mg/mL) a   
               
               
                   
                   
               
               
                   
                 acetate 
                 14.3  
               
               
                   
                 adipate 
                 9.5 
               
               
                   
                 citrate-crystalline 2 
                 11.5  
               
               
                   
                 glycolate 
                 26.5  
               
               
                   
                 hydrobromide-crystalline 1 
                 16 b   
               
               
                   
                 phosphate-crystalline 2 
                 1.8 
               
               
                   
                 phosphate-crystalline 8 
                 3.4 
               
               
                   
                   
               
               
                   
                   a Solubilities are calculated based on the total solvent used to give a solution; actual solubilities may be greater because of the volume of the solvent portions utilized or a slow rate of dissolution. 
               
               
                   
                   b Mean value of 22.5 mg/mL (2449-53-01) and 10.4 mg/mL (2449-84-01). 
               
            
           
         
       
     
     The most preferred methods of preparing the various polymorphic forms are given below. Each process description defines a further aspect of the present invention. 
     After each process, the resulting material was analyzed by XRPD and in some instances other analytical methods and designated as the titled material. 
     A. Preparation of L-Tartrate Salt Form A 
     20.1 mg of L-Tartrate salt was left to slurry in 20 mL of acetonitrile for 7 days under ambient conditions. 
     25B. Preparation of L-Tartrate Salt Form B 
     24.0 mg of L-Tartrate salt was left to slurry in 20 mL of ethyl acetate for 7 days under ambient conditions. 
     C. Preparation of Malonate Salt 
     24.5 mg malonate salt was left to slurry in 20 mL of methyl ethyl ketone for 7 days under ambient conditions. 
     D. Preparation of Tosylate Salt Form A 
     A filtered solution of 21.2 mg of tosylate salt in 1.1 mL of methanol was allowed to fast evaporate under ambient conditions. 
     E. Preparation of Tosylate Salt Form B 
     21.6 mg of tosylate salt was left to slurry in 20 mL of acetonitrile for 7 days under ambient conditions. 
     F. Preparation of Tosylate Salt Form C 
     44.5 mg of tosylate salt was left to slurry in 2 mL of iso-propanol for 4 days under ambient conditions. 
     G. Preparation of Tosylate Salt Form E 
     (a) 49.1 mg of tosylate salt was dissolved in 10 mL of 2,2,2-trifluoroethanol with sonication. 3 of 10 mL of 2,2,2-trifluoroethanol were added with sonication, the rest without. Solution was filtered then allowed to fast evaporate under ambient conditions in a hood. 
     (b) A filtered solution of 21.6 mg of tosylate salt in 5.0 mL of 2,2,2-trifluoroethanol was allowed to fast evaporate under ambient conditions. 
     H. Preparation of Tosylate Salt Form F 
     20.3 mg of tosylate salt was left to slurry in 20 mL of ethyl acetate for 7 days under ambient conditions. 
     I. Preparation of Tosylate Salt Form G 
     A filtered solution of tosylate salt in 4 mL of water was allowed to fast evaporate under ambient conditions. 
     J. Preparation of Tosylate Salt Form H 
     51.8 mg of tosylate salt was left to slurry in 2 mL of tetrahydrofuran (THF) for 4 days under ambient conditions. 
     K. Preparation of (1R)-10-Camphorsulfonate Salt 
     21.1 mg of camsylate salt was left to slurry in 10 mL of acetone under ambient conditions. 
     L. Preparation of Fumarate Salt 
     22.8 mg of fumarate salt was left to slurry in 20 mL of acetone for 7 days under ambient conditions. 
     M. Preparation of Acetate Salt Form 1 
     5 mL of methanol was dispensed into 50.0 mg of compound 2 with sonication. 10 μL of glacial acetic acid was dispensed into the solution with stirring. The solution was then allowed to fast evaporate to dryness under ambient conditions. 
     N. Preparation of Adipate Salt Form 1 
     Approximately 200 mg of compound 2 was dissolved in 5.5 mL of methanol with stirring on a hot plate. Temperature in the solution was measured at 55° C. 98.9 mg of adipic acid were dissolved in 0.3 mL of methanol at 55° C. The clear acid solution was added to the compound 2 solution with stirring. The solution was allowed to fast evaporate to dryness under ambient conditions in a hood. 
     O. Preparation of Glutaric Salt Form 1 
     51.1 mg of compound 2 was dissolved in 3.5 mL of methanol with sonication. 23.1 mg of glutaric acid were dissolved in 0.5 mL of methanol and added to the free base solution. 4 mL of ethyl acetate was added to the solution. The solution was allowed to fast evaporate to dryness under ambient conditions in a hood. 
     P. Preparation of Glycolic Salt Form 1 
     202.8 mg of compound 2 was dissolved in 6 mL of methanol with stirring on a hot plate. Temperature in the solution was measured at 50° C. 52.0 mg of glycolic acid were dissolved in 0.1 mL of methanol at 50° C. The clear acid solution was added to the free base solution. 6.1 mL of acetonitrile was added to the solution. The solution was allowed to slow cool under ambient conditions. 
     Q. Preparation of L-malic Salt Form 1 
     51.5 mg of compound 2 was dissolved in 4 mL of methanol with sonication. 23.8 mg of L-malic acid were dissolved in 0.1 mL of methanol and added to the free base solution. The solution was allowed to fast evaporate to dryness under ambient conditions in a hood. 
     R. Preparation of Citric Salt Crystalline Form 1 
     Preparation of the citric salt crystalline form 1 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in acetone at approximately 10 mg/mL, adding 0.1 mL of the solution in a well. Dilute citric acid solution was added (in methanol, 0.1M) to the well at slightly more than half a molar equivalent with respect to the active pharmaceutical ingredient (API). The plate was covered with a selfadhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient temperature orbital shaker for 11 days. Some evaporation occurred during mixing. The plate was left uncovered to complete evaporation under ambient conditions. The plate was then used in a recrystallization experiment. 25 μL of methanol was added to the well and the plate was loaded on an ambient-temperature orbital shaker at approximately 150 RPM for 1 hour. 75 μL of acetonitrile were added to the well C03. Finally, the plate was placed in a hood and allowed to evaporate until dry under ambient conditions. 
     S. Preparation of Citric Salt Crystalline Form 2 
     Approximately 200 mg of compound 2 was dissolved in 8 mL of acetone with stirring on a hot plate. Temperature in the solution was measured at 50° C. 141.9 mg of citric acid monohydrate were dissolved in 0.2 mL of methanol on a hot plate with stirring. The citric acid solution was added to the free base solution with stirring. Temperature in the solution was measured at 50° C. The solution was allowed to slow cool under ambient conditions. 
     T. Preparation of Gentisic Salt Crystalline Form 1 
     50.8 mg of compound 2 was dissolved in 3.5 mL of methanol with sonication. 26.9 mg of gentisic acid were dissolved in 0.5 mL of methanol and added to the free base solution. 4 mL of ethyl acetate was added to the solution. The solution was allowed to fast evaporate to dryness in a hood under ambient conditions. 
     U. Preparation of Gentisic Salt Crystalline Form 2 
     Preparation of the gentisic salt crystalline form 2 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in methanol at approximately 10 mg/mL, adding 0.1 mL of the solution in a well. Dilute gentisic acid solution was added (in methanol, 0.1M) to the well at slightly more than one molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 11 days. Some evaporation occurred during mixing. The plate was observed after 3 days by optical microscopy and returned to the shaker. The plate was left uncovered to complete evaporation under ambient conditions. The plate was then used in a recrystallization experiment. 75 μL of methanol was added to the well and the plate was loaded on an ambient-temperature orbital shaker at approximately 150 RPM for 1 hour. 75 μL of ethyl acetate were added to the well D06. Finally, the plate was placed in a hood and allowed to evaporate until dry under ambient conditions. The resulting material was analyzed by XRPD and designated as gentisate salt crystalline form 2. 
     V. Preparation of Maleic Salt Crystalline Pattern 1 
     Preparation of the maleic salt crystalline pattern 1 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in methanol at approximately 10 mg/mL, adding 0.1 mL of the solution in a well. Dilute maleic acid solution was added (in methanol, 0.1M) to the well at slightly more than half a molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was observed after 3 days by optical microscopy and returned to the shaker. The plate was left uncovered to complete evaporation under ambient conditions. The plate was then used in a recrystallization experiment. 75 μL of methanol was added to the well and the plate was loaded on an ambient-temperature orbital shaker at approximately 150 RPM for 30 minutes. 75 μL of ethyl acetate were added to the well C05. Finally, the plate was fast evaporated until dry under ambient conditions. 
     W. Preparation of Maleic Salt Crystalline 1 Plus Peaks 
     50.3 mg of compound 2, batch AB060109/1 was dissolved in 4 mL of methanol with sonication. 19.6 mg of maleic acid were dissolved in 0.2 mL of methanol and added to the free base solution. The solution was fast evaporated until dryness under ambient conditions in a hood. 
     X. Preparation of Hydrobromide Salt Crystalline Form 1 
     Preparation of the hydrobromide salt crystalline form 1 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in 2,2,2-trifluoroethanol at approximately 10 mg/mL, adding 0.1 mL of the solution in a well. Dilute HBr acid solution was added (in methanol, 0.1M) to the well at slightly more than one molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was observed after 3 days by optical microscopy and returned to the shaker. The plate was left uncovered to complete evaporation under ambient conditions. The plate was then used in a recrystallization experiment. 75 μL of methanol was added to the well and the plate was loaded on an ambient-temperature orbital shaker at approximately 150 RPM for 30 minutes. 75 μl, of toluene were added to the well A12. Finally, the plate was fast evaporated until dry under ambient conditions. 
     Y. Preparation of Hydrobromide Salt Crystalline Form 2 
     Preparation of the hydrobromide salt crystalline form 2 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in acetone at approximately 10 mg/mL, adding 0.1 mL of the solution in a well. Dilute HBr acid solution was added (in methanol, 0.1M) to the well at slightly more than one molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 0.8 days. Some evaporation occurred during mixing. The plate was left uncovered to complete evaporation under ambient conditions. The plate was then used in a recrystallization experiment. 75 μL of methanol was added to the well and the plate was loaded on an ambient-temperature orbital shaker at approximately 150 RPM for 30 minutes. 75 μL of acetonitrile were added to the well A01. Finally, the plate was fast evaporated until dry under ambient conditions. 
     Z. Preparation of Hydrobromide Salt Crystalline Form 3 
     50.2 mg of compound 2 was dissolved in 6 mL of acetone with sonication. 18.7 μL of HBr acid were dispensed into the free base solution with sieving. The solution was fast evaporated until dryness under ambient conditions. 
     AA. Preparation of Succinate Salt Crystalline Form 1 
     Preparation of the succinate salt crystalline form 1 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in methanol at approximately 10 mg/mL, adding 0.1 mL of the solution in a well. Dilute succinic acid solution was added (in methanol, 0.1M) to the well E06 at slightly more than half a molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was left uncovered to complete evaporation under ambient conditions. 
     BB. Preparation of Succinate Salt Crystalline Form 2 
     Preparation of the succinate salt crystalline form 2 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in 2,2,2-trifluoroethanol at approximately 10 mg/mL, adding 0.1 mL of the solution in well E12. Dilute succinic acid solution was added (in methanol, 0.1M) to the well at slightly more than half a molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was left uncovered to complete evaporation under ambient conditions. The plate was then used in a recrystallization experiment. 75 μL of methanol was added to the well and the plate was loaded on an ambient-temperature orbital shaker at approximately 150 RPM for 30 minutes. 75 μL of toluene were added to the well. Finally, the plate was fast evaporated until dry under ambient conditions. 
     CC. Preparation of Succinate Salt Crystalline Form 3 
     102.4 mg of compound 2, batch AB060109/1 was dissolved in 8 mL of 2,2,2-trifluoroethanol. 41.3 mg of succinic acid was dissolved in 0.8 mL of methanol and added to the free base solution. 4.4 mL of the solution were taken out for another sample. The remaining solution was fast evaporated until dryness under ambient conditions in a hood. 
     DD. Preparation of Phosphoric Salt Crystalline Form 1 
     Preparation of the phosphoric salt crystalline form 1 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in 2,2,2-trifluoroethanol at approximately 10 mg/mL, adding 0.1 mL of the solution in well G12. Dilute phosphoric acid solution was added (in methanol, 0.1M) to the well at slightly more than a third of a molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was left uncovered to complete evaporation under ambient conditions. 
     EE. Preparation of Phosphoric Salt Crystalline Form 2 
     Preparation of the phosphoric salt crystalline form 2 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in acetone at approximately 10 mg/mL, adding 0.1 mL of the solution in well G02. Dilute phosphoric acid solution was added (in methanol, 0.1M) to the well at slightly more than a third of a molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was left uncovered to complete evaporation under ambient conditions. 
     FF. Preparation of Phosphoric Salt Crystalline Form 3 
     Preparation of the phosphoric salt crystalline form 3 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in methyl ethyl ketone at approximately. 10 mg/mL, adding 0.1 mL of the solution in well G07. Dilute phosphoric acid solution was added (in methanol, 0.1M) to the well at slightly more than a third of a molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was left uncovered to complete evaporation under ambient conditions. The plate was then used in a recrystallization experiment. 75 μL of methanol was added to the well and the plate was loaded on an ambient-temperature orbital shaker at approximately 150 RPM for 30 minutes. 75 μL of isopropanol were added to the well. Finally, the plate was fast evaporated until dry under ambient conditions. 
     GG. Preparation of Phosphoric Salt Crystalline Form 4 
     Preparation of the phosphoric salt crystalline form 4 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving compound 2 in methyl ethyl ketone at approximately 10 mg/mL, adding 0.1 mL of the solution in well G08. Dilute phosphoric acid solution was added (in methanol, 0.1M) to the well at slightly more than a third of a molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was left uncovered to complete evaporation under ambient conditions. The plate was then used in a recrystallization experiment. 75 μL of methanol was added to the well and the plate was loaded on an ambient-temperature orbital shaker at approximately 150 RPM for 30 minutes. 75 μL of isopropanol were added to the well. Finally, the plate was fast evaporated until dry under ambient conditions. 
     HH. Preparation of Phosphoric Salt Crystalline Form 5 
     49.7 mg of Compound 2 was dissolved in 5 mL of methanol with sonication. Dispensed 11.5 μL of phosphoric acid into the free base solution with stirring. The solution was allowed to fast evaporate until dryness under ambient conditions. 
     II. Preparation of Phosphoric Salt Crystalline Form 6 
     1 mL of Compound 2 was dissolved in 1 mL of methanol. The solution was stirred on a RT plate at 60 RPM. 73 μL of phosphoric acid was added. The experiment was performed in a dark fume hood. 
     JJ. Preparation of Phosphoric Salt Crystalline Form 7 
     10 mg of Compound 2 was dissolved in 5 mL of methanol and 1 mL of 2,2,2-trifluoroethanol. The solution was stirred on a RT plate at 60 RPM. 73 μL of phosphoric acid was added. The experiment was performed in a dark fume hood. A white precipitate (solids) was instantly generated upon acid addition. 
     KK. Preparation of Phosphoric Salt Crystalline Form 8 
     103 mg of Compound 2 was dissolved in 10 mL of methanol with sonication. 22.6 μL of 85% phosphoric acid were added to the free base solution with stirring. The solution was allowed to fast evaporate until dryness under ambient conditions in a hood. 
     LL. Preparation of Sulfuric Salt Crystalline Form 1 
     64 mg of Compound 2 was dissolved in 2 mL of methanol. 98 mg of sulfuric acid was dissolved in 1 mL of methanol and added to the free base solution. The solution was shaken then allowed to fast evaporate until dryness under ambient conditions. 
     MM. Preparation of Sulfuric Salt Crystalline Form 2 
     Preparation of the sulfuric salt crystalline form 2 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving Compound 2 in methanol at approximately 10 mg/mL, adding 0.1 mL of the solution in well F06. Dilute sulfuric acid solution was added (in methanol, 0.1M) to the well at slightly more than half the molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was observed after 3 days by optical microscopy and returned to the shaker. The plate was left uncovered to complete evaporation under ambient conditions. 
     NN. Preparation of Sulfuric Salt Crystalline Form 3 
     Preparation of the sulfuric salt crystalline form 3 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving Compound 2 in acetone at approximately 10 mg/mL, adding 0.1 mL of the solution in well F06. Dilute sulfuric acid solution was added (in methanol, 0.1M) to the well, at slightly more than half the molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 0.8 days. Some evaporation occurred during mixing. The plate was observed after 3 days by optical microscopy and returned to the shaker. The plate was left uncovered to complete evaporation under ambient conditions. 
     OO. Preparation of Sulfuric Salt Crystalline Form 4 
     Preparation of the sulfuric salt crystalline form 4 was carried out in a 96-well polypropylene plate using the following procedure. A solution was prepared by dissolving Compound 2 in methanol at approximately 10 mg/mL, adding 0.1 mL of the solution in well F05. Dilute sulfuric acid solution was added (in methanol, 0.1M) to the well at slightly more than half the molar equivalent with respect to the API. The plate was covered with a self-adhesive aluminum foil cover and allowed to mix at approximately 25 RPM on an ambient-temperature orbital shaker for 8 days. Some evaporation occurred during mixing. The plate was observed after 3 days by optical microscopy and returned to the shaker. The plate was left uncovered to complete evaporation under ambient conditions. 
     PP. Preparation of Sulfuric Salt Crystalline Form 5 
     64 mg of Compound 2 was dissolved in 5 mL of acetone. 99 mg of sulfuric acid was dissolved in 1 mL of acetone and added to the free base solution. The solution was shaken and sonicated, then allowed to fast evaporate until dryness under ambient conditions. 
     QQ. Preparation of Sulfuric Salt Crystalline Form 6 
     49.9 mg of Compound 2 was dissolved in 4 mL of methanol with sonication. 9.4 μL of sulfuric acid were added to the free base solution. 4 mL of ethyl acetate were added to the free base solution. The solution was allowed to fast evaporate until dryness under ambient conditions. 
     RR. Preparation of Sulfuric Salt Crystalline Form 7 
     62 mg of Compound 2 was dissolved in 5 mL of acetone. 99 mg of sulfuric acid was dissolved in 1 mL of acetone and added to the free base solution. The solution was shaken and sonicated, then allowed to fast evaporate until dryness under ambient conditions. 
     41 mg of the material were weighed into a vial. 2 mL of acetone were added. The mixture was shaken and sonicated then slurried at ambient temperature. 
     SS. Preparation of Sulfuric Salt Crystalline Form 8 
     1 mL of Compound 2 was dissolved in 1 mL of 2,2,2-trifluoroethanol. The solution was stirred on a RT plate at 60 RPM. 73 μL of sulfuric acid was added. After a few minutes, the stir rate was briefly increased to 200 RPM, then reduced back to 60 RPM. The experiment was performed in a dark fume hood. 
     TT. Preparation of Compound 2 Free Base Form A 
     30.9 mg of compound 2 was dissolved in 1 mL of acetonitrile with sonication. The solution was left to slurry for 7 days under ambient conditions. 
     It will be appreciated that the invention may be modified within the scope of the appended claims.