Antifungal compounds and processes for making
The present invention relates to polymorphic forms of compound 1 or 1a and processes for preparing compound 1 and 1a polymorphs, which are useful as antifungal agents. In particular, the invention seeks to provide a new methodology for preparing polymorphs of compound 1 and substituted derivatives thereof.
1. An anhydrous polymorph of a compound of formula 1,
wherein the polymorph has the crystal structure as shown in FIG. 9 .
2. A process to prepare an anhydrous polymorph of compound 1:
comprising suspending a compound of formula 1 in a solvent and isolating any solid material.
3. The process of claim 2 , wherein the compound suspended in the solvent is in one of an amorphous, solvate, or hydrate form.
4. The process of claim 2 , wherein the solvent is an organic solvent.
5. The process of claim 2 , wherein the solvent is a C 3 -C 10 alcohol.
6. The process of claim 5 , wherein the solvent is n-propanol, i-propanol, n-butanol, i-butanol, s-butanol, or t-butanol.
7. The process of claim 2 , comprising two or more solvents.
8. The process of claim 7 , wherein one solvent is a C 3 -C 10 alcohol and one solvent is a hydrocarbon.
9. The process of claim 8 , wherein the alcohol solvent is n-propanol, propanol, n-butanol, i-butanol, s-butanol, or t-butanol.
10. The process of claim 8 , wherein the hydrocarbon solvent is n-pentane, n-heptane or n-hexane, cyclohexane, or methylcyclohexane.
11. The process of claim 8 , wherein one solvent is i-propanol and one solvent is n-heptane.
12. The process of claim 2 , wherein the isolated solid material is dried at a temperature of 30° C. or higher.