Potassium Fluoride → HCID 118093615, compound

Participants

Reaction Conditions

Reaction Steps

Add potassium fluoride (1.82 g, 31.33 mmol) to a solution of 1-[4-[6-(aminomethyl)-2-methyl-pyrimidin-4-yl]oxyphenyl]-N-methyl-methanesulfonamide (11.1 g, 24.10 mmol) and 2,5-dichloropyrimidine (4.31 g, 28.92 mmol) in DMSO (111 mL). Heat the reaction mixture at 120° C. for two hours. Thereafter cool the mixture to room temperature; add water (200 mL), and extract with EtOAc (3×200 mL). Combine the organic extracts; sequentially wash the organic extracts with water (300 mL) then brine (300 mL); dry over sodium sulfate; filter; and concentrate the filtrate under reduced pressure to provide title compound as a crude material. Purify the title compound using silica gel chromatography eluting with a gradient of hexane/EtOAc (1:1) to EtOAc (100%). Collect the relevant fractions containing the title compound and concentrate the fractions. Dissolve the resulting material in THF (200 mL) and EtOAc (300 mL), then add SiliaMetS® Thiol (9.2 g) to remove traces of palladium. Stir the mixture for 2 hr at 55° C. Filter the mixture at 55° C.; collect the filtrate; and evaporate the solvent to provide a solid. Triturate the solid with cold EtOAc (20 mL); collect the solid by filtration; and dry the solid under reduced pressure to provide the title compound as a white solid (8 g, 75%). MS (m/z): 435 (M+1).

Provenance & Evidence