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 ethanol solvate polymorph of a compound of formula 1,
characterized by at least one of:
(i) a powdered X-ray diffraction pattern having two or more peaks expressed in degrees 2-theta±0.2° and selected from peaks delineated in the pattern of FIG. 2 ;
or
(ii) a DSC thermogram showing an endotherm at about 65-75° C.
2. The compound of claim 1 , characterized by a powdered X-ray diffraction pattern having peaks expressed in degrees 2-theta±0.2° at each of about 9.1, 12.2, 14.1, 19.2, 24.1.
3. The compound of claim 1 , characterized by a melting point of about 65-75° C.
4. The compound of claim 1 , having about 2% to 3% water therein.
5. A process to prepare an ethanol solvate polymorph of compound 1,
comprising suspending a compound of formula 1 or 1a in a solvent and isolating any solid material.
6. The process of claim 5 , wherein the compound suspended in the solvent is in one of an amorphous, solvate, or hydrate form.
7. The process of claim 5 , wherein the solvent is an organic solvent.
8. The process of claim 5 , wherein the solvent is ethanol.
9. The process of claim 5 , comprising two or more solvents.
10. The process of claim 5 , wherein one solvent is ethanol and one solvent is water.
11. The process of claim 5 , wherein the isolated solid material is dried at a temperature of 30-60° C.
12. An ethanol solvate polymorph of a compound 1,
wherein the polymorph has the crystal structure as shown in FIG. 10 .