Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides
View Patent ↗The invention relates to crystalline peptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions. This invention also relates to methods for the preparation of amino acid keto-epoxides. Specifically, allylic ketones are stereoselectively converted to the desired keto epoxides.
1. Crystalline compound 1 having the formula:
and peaks as determined by XRPD at 2θ values 6.10; 8.10; 9.32; 10.10; 11.00; 12.14; 122.50; 13.64; 13.94; 17.14; 17.52; 18.44; 20.38; 21.00; 22.26; 23.30; 24.66; 25.98; 26.02; 27.84; 28.00; 28.16; 29.98; 30.46; 32.98; 33.22; 34.52; and 39.46.
2. Crystalline compound 1 having the formula:
and a DSC thermogram as shown in FIG. 1 .
3. Crystalline compound 1 having the formula:
and an XRPD pattern as shown in FIG. 2 .
4. The crystalline compound of claim 1 having an XRPD pattern as shown in FIG. 2 .
5. The crystalline compound 1 of claim 1 wherein the melting temperature is 212° C.
6. The crystalline compound 1 of claim 2 wherein the melting temperature is 212° C.
7. The crystalline compound 1 of claim 3 wherein the melting temperature is 212° C.
8. The crystalline compound 1 of claim 4 wherein the melting temperature is 212° C.