GSK2269557  is a potent inhalable PI3Kd-selective inhibitor being developed by GSK forthe treatment of inflammatory airway diseases. Here we are reporting an efficient route to this compound.   Starting from methyl 6-bromo-1H-indazole-4-carboxylate 1  , the key oxazole intermediate 5  was obtained through aminolysis, Dess-Martin oxidation, dehydration and subsequent benzylic oxidation. Reductive amination followed by protecting group manipulation and Suzuki-coupling afforded the title compound GSK2269557   in24.8% overall yield after eight steps. Our route avoids the use of expensive starting material and toxic organtin reagent in the key Stille-coupling in the prior report. In addition, all intermediates could be easily purified by slurrying in proper solvents and no column chromatography was needed.

Novel synthetic method of GSK2269557

248th National Meeting (2014)

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