Solid forms of a glyt1 inhibitor

Abstract

Disclosed are solid forms of an inhibitor of glycine transporter-1 (GlyT1). The invention also relates to methods of making these solid forms, pharmaceutical compositions comprising these solid forms, and their use for medical conditions responsive to treatment with an inhibitor of glycine transporter-1.

1 . A solid Form I of Coumpound  1  having the structural formula: 
       
         
           
           
               
               
           
         
         wherein the Form I of Coumpound  1  is characterized by: 
         at least three XRPD peaks at 2Θ angles selected from 4.6°, 10.0°, 16.7°, 18.0°, 19.0°, 20.0° and 22.7°; or 
         at least three  13 C solid-state nuclear magnetic resonance peaks at chemical shifts selected from 131.5 ppm, 127.2 ppm, 28.7 ppm, and 25.7 ppm; or 
         at least three  19 F solid-state nuclear magnetic resonance peaks at chemical shifts selected from −64.3, −64.8, −65.9, −66.8, −78.0, −78.5, −79.3, and −80.0 ppm. 
       
     
     
         2 . The solid Form I of Coumpound  1  according to  claim 1 , characterized by XRPD peaks at 2Θ angles selected from 4.6°, 10.0°, 16.7°, 18.0°, 19.0°, 20.0° and 22.7°. 
     
     
         3 . The solid Form I of Coumpound  1  according to  claim 1 , characterized by  13 C solid-state nuclear magnetic resonance peaks at chemical shifts selected from 131.5 ppm, 127.2 ppm, 28.7 ppm, and 25.7 ppm. 
     
     
         4 . The solid Form I of Coumpound  1  according to  claim 1 , characterized by  19 F solid-state nuclear magnetic resonance peaks at chemical shifts selected from −64.3, −64.8, −65.9, −66.8, −78.0, −78.5, −79.3, and −80.0 ppm. 
     
     
         5 - 7 . (canceled) 
     
     
         8 . A solid Form III of Coumpound  1  having the structural formula: 
       
         
           
           
               
               
           
         
         wherein the Form III of Coumpound  1  is characterized by: 
         at least three XRPD peaks at 20 angles selected from 4.8°, 9.7°, 10.3°, 13.9°, and 24.6°; or 
         at least three  13 C solid-state nuclear magnetic resonance peaks at chemical shifts selected from 156.6 ppm, 134.2 ppm, 46.0 ppm, 25.5 ppm, and 14.3 ppm. 
       
     
     
         9 . The solid Form III of Coumpound  1  according to  claim 8 , characterized by XRPD peaks at 2Θ angles selected from 4.8°, 9.7°, 10.3°, 13.9°, and 24.6°. 
     
     
         10 . The solid Form III of Coumpound  1  according to  claim 8 , characterized by  13 C solid-state nuclear magnetic resonance peaks at chemical shifts selected from 156.6 ppm, 134.2 ppm, 46.0 ppm, 25.5 ppm, and 14.3 ppm. 
     
     
         11 . A method of making Form I of Coumpound  1  according to  claim 1 , comprising,
 (a) heating Coumpound  1  and tert-butyl methyl ether (TBME) or water to provide a slurry; 
 (b) cooling the slurry of step (a); and 
 (b) collecting the resulting solids as Form I of Compound  1 . 
 
     
     
         12 . A method of making Form II of Coumpound  1  according to claim  5 , comprising:
 (a) heating a mixture of Coumpound  1  and 2-propanol to 70° to provide a solution; 
 (b) filtering the solution of step (a); 
 (c) cooling the filtrate from step (b) to 55° C.; 
 (d) treating the cooled solution of step (c) with water; 
 (e) cooling the water-treated mixture of step (d) to 20° C.; and 
 (f) collecting the resulting solids as Form II of Compound  1 . 
 
     
     
         13 . A method of making Form III of Coumpound  1  according to  claim 8 , comprising:
 (a) heating a mixture of Coumpound  1  (Form II) and methanol to 50-55° C. to provide a solution; 
 (b) concentrating the solution of step (a) at 40-45° C.; 
 (c) cooling the concentrated solution from step (b) to 25° C.; and 
 (d) collecting the resulting solids as Form III of Compound  1 . 
 
     
     
         14 . A pharmaceutical composition comprising the solid form of the compound according to  claim 1 , optionally together with one or more inert carriers and/or diluents. 
     
     
         15 . (canceled) 
     
     
         16 . A pharmaceutical composition comprising the solid form of the compound according to  claim 8 , optionally together with one or more inert carriers and/or diluents. 
     
     
         17 . A method of treating and/or preventing a neurological or psychiatric disorder comprising administering a pharmaceutically effective amount of Coumpound  1  of according to  claim 1  to a patient in need thereof. 
     
     
         18 . The method according to  claim 17 , wherein the neurological or psychiatric disorder is selected from the group consisting of schizophrenia, cognitive impairment associated with schizophrenia, and Alzheimer's Disease. 
     
     
         19 . A method of treating and/or preventing a neurological or psychiatric disorder comprising administering a pharmaceutically effective amount of Coumpound  1  of according to claim  5  to a patient in need thereof. 
     
     
         20 . The method according to  claim 19 , wherein the neurological or psychiatric disorder is selected from the group consisting of schizophrenia, cognitive impairment associated with schizophrenia, and Alzheimer's Disease. 
     
     
         21 . A method of treating and/or preventing a neurological or psychiatric disorder comprising administering a pharmaceutically effective amount of Coumpound  1  of according to  claim 8  to a patient in need thereof. 
     
     
         22 . The method according to  claim 21 , wherein the neurological or psychiatric disorder is selected from the group consisting of schizophrenia, cognitive impairment associated with schizophrenia, and Alzheimer's Disease.