LFA-1 inhibitor and methods of preparation and polymorph thereof
Methods of preparation and purification of a compound of Formula I, intermediates thereof, a polymorph thereof, and related compounds are disclosed. Formulations and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed.
1. A crystalline form of the compound of Formula I:
or a salt thereof,
which is crystalline Form II.
2. The crystalline form of claim 1 , having an X-ray powder diffraction pattern comprising the following peaks, in terms of 2-theta, at about 10.8, 16.4, and 21.8 degrees.
3. The crystalline form of claim 1 , wherein having an X-ray powder diffraction pattern substantially as shown in FIG. 4 .
4. The crystalline form of claim 1 , having a differential scanning calorimetry thermogram (DSC) comprising an endothermic peak at about 37.8° C.
5. The crystalline form of claim 1 , the having a differential scanning calorimetry thermogram (DSC) comprising a melting transition at about 155.5° C.
6. The crystalline form of claim 1 , having a differential scanning calorimetry thermogram (DSC) substantially as shown in FIG. 7 .
7. The crystalline form of claim 1 , having a thermogravimetric analysis (TGA) substantially as shown in FIG. 8 .
8. The crystalline form of claim 1 , having a water content of about 3.2 wt % by Karl Fisher titration.
9. A composition comprising the crystalline form of claim 1 .
10. The composition of claim 9 , wherein said composition comprises at least one pharmaceutically acceptable carrier.
11. The composition of claim 9 , wherein the composition is at least about 50% by weight Form II.
12. The composition of claim 9 , wherein the composition is at least about 5% by weight Form II.
13. A process for preparing the crystalline form of claim 1 , comprising combining the compound of Formula I with acetone and n-heptane.
14. The crystalline form of claim 1 , prepared by a process comprising combining the compound of Formula I with acetone and n-heptane.
15. The crystalline form of claim 1 which is a monohydrate.