利托那韦的合成新方法

A Novel Synthetic Method of Ritonavir

建立了利托那韦的合成新方法。N-{N-甲基-N-[(2-异丙基-4-噻唑基)甲基]氨基羰基}-L-缬氨酸(1)与(2S,3S,5S)-5-氨基-2-{N-[(5-噻唑基)-甲氧羰基]氨基}-1,6-二苯基-3-羟基己烷在3-(二乙氧基磷酰氧基)-1,2,3-苯并三嗪-4-酮催化下于室温经缩合反应合成了利托那韦,其结构经1H NMR,13C NMR,MS和元素分析确证。在最佳反应条件[1 0.2 mol,DEPBT 0.25 mmol,二氯甲烷为溶剂,三乙胺为缚酸剂,于室温反应过夜]下,收率72.6%。

A novel synthetic method of Ritonavir was established. Ritonavir was synthesized by reaction of（S）-2-{ 3-[（2-isopropylthiazol-4-yl） methyl]-3-methylureido}-3-methylbutanoic acid with thiazol-5-ylmethyl（2S,3S,5S）-5-amino-3-hydroxy-1,6-diphenylhexan-2-ylcarbamatecatalyzed using 3-（diethoxyphosphoryloxy）-1,2,3-benzotriazin-4（3H）-one as the catalyst and triethylamine as the acid-binding agent. The structure was confirmed by ^1 H NMR,^13 C NMR,MS and elemental analysis.Under the optimum reaction conditions[1 0. 2 mol,DEPBT 0. 25 mmol,dichloromethane as the solvent,triethylamine as the acid-binding agent,at room temperature for one night],the yield was 72. 6%.