Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides

摘要

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.

主权项

1. A method for preparing a crystalline salt of a compound of Formula (II) wherein the salt is a citrate salt; and the method comprises (i) preparing a solution of a compound of Formula (II) in an organic solvent; (ii) adding citric acid; (iii) bringing the solution to supersaturation to cause formation of crystals; and (iv) isolating the crystals, wherein said crystalline compound has 2θ values of 4.40; 7.22; 9.12; 12.36; 13.35; 14.34; 15.54; 16.14; 16.54; 17.00; 18.24; 18.58; 19.70; 19.90; 20.30; 20.42; 21.84; 22.02; 23.34; 23.84; 24.04; 24.08; 24.48; 24.76; 25.48; 26.18; 28.14; 28.20; 28.64; 29.64; 31.04; 31.84; 33.00; 33.20; 34.06; 34.30; 34.50; 35.18; 37.48; 37.90; and 39.48.