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. A 1.5 hydrate 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. 5 ; or
(ii) a DSC thermogram showing an endotherm at about 85° C.
2. A process to prepare a 1.5 hydrate polymorph of compound 1:
comprising suspending a compound of formula 1 in a solvent and isolating any solid material.
3. 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 7.9, 8.9, 16.2, 22.6, 24.2, 26.6, 28.0.
4. The compound of claim 1 , wherein the compound is essentially solvent free.
5. The compound of claim 1 , wherein the compound has 0.1-0.5% weight solvent.
6. The process of claim 2 , wherein the compound suspended in the solvent is in one of an amorphous, solvate, or hydrate form.
7. The process of claim 2 , wherein the solvent is an organic solvent.
8. The process of claim 2 , wherein the solvent is a C 3 -C 10 alcohol.
9. The process of claim 2 , comprising two or more solvents.
10. The process of claim 2 , wherein one solvent is a C 3 -C 10 alcohol and one solvent is water.
11. The process of claim 2 , wherein the isolated solid material is dried at a temperature of 30-60° C.