A solution of 2-(chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (55 mg, 0.1 mmol) in acetonitrile (0.5 ml) was added to 4,4-dimethylpiperidine hydrochloride (0.11 mmol, available from Microchemistry Ltd). DIPEA was then added (0.026 ml, 0.15 mmol), followed by sodium iodide (13 mg). The vial was capped and the stirred solution heated to 70° C. for 18 h. Potassium trimethylsilanolate (26 mg) was dissolved in THF (0.3 ml) and added to the vessel, which was then stirred at room temperature for 21 h, then heated at 50° C. for 3 h. A further equivalent of potassium trimethylsilanolate was added as a solution in THF (150 ul) and the mixture was heated at 50° C. for a further 18 h. The solution was quenched with aqueous acetonitrile (500 ul, 50:50) and neutralised. Solvent was removed by blowdown. The residue was dissolved in DMSO 0.5 mL and purified by Mass Directed AutoPrep HPLC (Method F). The solvent was removed by vacuum centrifugation to give the title compound (7 mg). LCMS (Method C) Rt=1.69 min, MH+=485.
