CPC A61K 31/4704 (2013.01) [A61K 9/0014 (2013.01); A61K 9/0019 (2013.01); A61K 9/0053 (2013.01); A61K 31/47 (2013.01); A61K 31/706 (2013.01); A61K 45/06 (2013.01); A61P 31/14 (2018.01); C07D 215/52 (2013.01); C07B 2200/13 (2013.01)] | 14 Claims |
1. A method of making a crystal comprising at least 80% polymorphic form C of brequinar sodium salt, the method comprising the steps of:
combining a solid form of brequinar acid, sodium hydroxide (NaOH), and a solvent comprising isopropanol and water to produce a solution and removing insoluble material from the combined brequinar acid, NaOH, and solvent;
crystallizing brequinar sodium salt from the solution to produce a crystal comprising polymorphic form C of brequinar sodium salt, wherein the crystallizing step comprises sequentially performing the steps of:
adding a seed crystal of polymorphic form C of brequinar sodium salt to the solution to produce a seeded mixture;
adding n-heptane to the seeded mixture to produce an alkane-containing mixture and incubating the alkane-containing mixture at from about 15° C. to about 35° C.; and
removing the solvent from the seeded mixture at a temperature below ambient temperatures, wherein the removing step results in a crystal comprising at least 80% polymorphic form C of brequinar sodium salt as measured by X-ray Diffraction (XRD).
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