维格列汀的合成工艺改进

Process Improvement on Synthesis of Vildagliptin

以L-脯氨酰胺为起始原料,经氯乙酰氯酰化及三聚氰氯脱水一锅法制得(S)-N-氯乙酰基-2-氰基吡咯烷(4);4与3-氨基-1-金刚烷醇经亲核取代反应合成了维格列汀,总收率75%,其结构经1H NMR和MS(ESI)确证。

（S） -N-chloracetyl-2-cyanopyrrolidines （4） was prepared by the reaction of acetylation reac- tion and dehydration reaction using L-prolinamide as starting material. Vildagliptin with total yield of 75% was synthesized by nucleophilic substitution of 4 with 3-amino-l-adamantanol. The structure was confirmed by 1H NMR and MS（ESI）.