度鲁特韦的合成工艺优化研究

Research on optimization for synthetic process of dolutegravir

以4-甲氧基乙酰乙酸甲酯为原料,经过六步反应合成了度鲁特韦关键中间体6,总体收率为18. 7%。六步反应中,仅仅在第四步和第六步通过洗涤滤饼的简单操作纯化了目标产物,其余步骤均采用粗产品进行下一步投料,极大地简化操作。通过对中间物7以及度鲁特韦终产物进行了重结晶纯化操作,提高了度鲁特韦原料药的纯度。

The key intermediate 6 of dolutegravir was synthesized through 6 steps of reaction starting from methyl 4-methoxyacetoacetate as raw material. The total yield of the 6 steps was up to 18.7%. In the above steps,only the products of the fourth and sixth step were purified through simply washing filter cake, whereas the products of the rest steps were raw product without special purification for next step. Through recrystallization, the purity of final product dolutegravir was enhanced to meet the requirements of industrial production.