Preparation method of cobimetinib

The invention discloses a preparation method of cobimetinib (Cobimetinib, XL518, GDC-0973) (I). The method includes the preparation steps of preparing an intermediate [2-oxo-2-((2S)-1-t-butyloxycarboryl-2-based]acetate through acyl cyanide formation, hydrolysis, esterification and Boc prortection with (2S)-2-pipecolic acid as the raw material, preparing an intermediate (2S)-1-t-butyloxycarboryl-2-(3-azetidinol-3-based)piperidine by conducting the addition reaction, the reduction action and the cyclization reaction on the intermediate body, and making the intermediate (2S)-1-t-butyloxycarboryl-2-(3-azetidinol-3-based)piperidine and a side chain subjected to a condensation reaction to obtain the cobimetinib (I). According to the preparation method, raw materials can be easily obtained, the process is simple, and the method is economical, environmentally friendly and suitable for industrialized production.