Method for Preparation of N-Acetyl Cysteine Amide and Derivatives Thereof

Presented herein are methods for making, isolating, and purifying N-acetylcysteine amide, (2R,2R′)-3,3′-disulfanediyl bis(2-acetamidopropanamide, diNACA), intermediates and derivatives thereof comprising: alternatively contacting cystine with methanol and a chlorinating reagent to form an organic solution containing L-cystine dimethylester dihydrochloride; combining dried or undried L-cystine dimethylester dihydrochloride with a triethylamine, an acetic anhydride, and an acetonitrile to form a di-N-acetylcystine dimethylester; mixing dried di-N-acetylcystine dimethylester with ammonium hydroxide to form a di-N-acetylcystine amide (diNACA); and separating dried di-N-acetylcystine dimethylester into N-acetylcysteine amide with dithiothreitol, triethylamine, and an alcohol.