HIV整合酶抑制剂雷特格韦的合成

Synthesis of raltegravir as the HIV ingretase inhibitor

目的探究雷特格韦的合成方法。方法以2-氨基-2-甲基丙腈盐酸盐为起始原料,经过苄氧羰基保护氨基、由腈转化成肟、环合形成嘧啶、N-甲基化、酯的胺解、氢气还原脱保护、再经酰化缩合成酰胺等一系列反应制备得到雷特格韦。结果与结论目标产物雷特格韦及部分中间体的化学结构经1H-NMR和MS确证,总收率为25.29%（以2-氨基-2-甲基丙腈盐酸盐计）,高于文献收率（12.0%）。

Objective To find a route to synthesize raltegravir. Methods Using 2-amino-2-methyl acrylic nitrile hydrochlodide as starting material,raltegravir was synthesized by a series of reactions like amino group protection,converting nitrile into oxime,cyclization,N-methylation,ammonolysis,deprotection and amidation. Results and Conclusions Raltegravir and parts of intermediates were characterized by IR,MS,1H-NMR spectra,and total yield was 25. 29%（ with 2-amino-2-methylacrylic nitrile hydrochloride）,which was higher than that of report in literature（12. 0%）.