Optimization Study On The Synthesis Process Of SB-590885

Cancer is the second in mortality of most common disease,which poses a great threat to the health of human beings around the world.The Ras/Raf/MEK/ERK signaling cascade has received considerable attention in mitogen activated protein kinase(MAPK)mediated pathways.Among them,B-Raf is one of the most concerned targets because of its relatively high mutation rate in tumors.SB-590885 is a high selective B-Raf kinase inhibitor,SB-590885 has better selectivity for B-Raf compared to A-Raf or C-Raf.SB-590885 can effectively target selection mutants,and reduce the dependent adherent growth of the melanoma cell line by interaction.Currently SB-590885 is still in preclinical studies.It is found that the existing synthetic routes are protected by foreign patents.And the operation is cumbersome,the reaction conditions are harsh,and the yield is low.Therefore,the research group is entrusted by the cooperative enterprise to conduct experimental research on its intermediates and preparation processes,laying the foundation for the preparation of related derivatives and the pilot scale.In this paper,three synthetic routes of SB-590885 was designed and their synthesis conditions were investigated.Finally,a synthetic route suitable for the pilot experiments was determined,etc using 4-bromopyridine hydrochloride,5-bromofluorenone and p-hydroxybenzaldehyde as raw materials.Compared with the reported methods,this route has the advantages of low cost,simple operation,mild conditions,etc.The total yield is 9.64%,the HPLC purity of the final product is more than 99%,and the target compound structure is characterized by MS and ~1H-NMR.