A concise and efficient synthesis of vildagliptin

Abstract An original synthesis of vildagliptin (( S )-1-[2-(3-hydroxyadamantan-1-ylamino)acetyl]pyrrolidine-2-carbonitrile), a powerful DPP-4 inhibitor, was developed. Vildagliptin was assembled from 3-amino-1-adamantanol, glyoxylic acid and l -prolinamide in a 4-step reaction sequence with the isolation of only two intermediates. The procedure is competitive with existing protocols, leading to vildagliptin in 63% overall yield.