常山酮的合成方法研究

Study on the Synthetic Technique of Halofuginone

本文对常山酮(halofuginone)的合成方法进行了研究和改进,以2-甲基-3-羟基吡啶为起始原料,其甲基化产物与乙腈加成后经Rh/Al2O3选择性还原得(3-甲氧基-2-哌啶基)-丙酮,再经溴代、N-保护后与6-氯-7-溴-4(3H)-喹唑啉酮偶联,产物经水解脱保护得目标化合物6-氯-7-溴-3-(3-(3-羟基-2-哌啶基)-丙酮基)-4(3H)-喹唑啉酮氢溴酸盐,通过6步反应制得了常山酮,总收率为11.6%,为常山酮的工业化生产提供了可能。目标产物和各步中间体结构经MS1、H NMR和13CNMR确证。

The synthesis of Halofuginone was researched and improved in this artical. Halofuginone was synthesized from 2-methylpyridin-3-ol by methylation addition and selective catalytic reduction to give 1- （3-methoxypiperidin-2-yl）propan-2-one, which was subjected to bromination, N-protection, substitution to afford allyl 2-（ 3-（ 7-bromo-6-chloro-4-oxo-quinazolin-3 （ 4H）-yl）-2-oxopropyl）-3-methoxypiperidine-1- carboxylate, and finally hydrolation with acid to give the product. The chemical structures of halofuginone and its intermediate were confirmed by 1H NMR, 13 C NMR and MS. The total yield ratio of production was 11.7%. The new synthetic route provided the possibility for industrial production of Halofuginone.