Sodium Iodide → N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

Participants

Reaction Conditions

Reaction Steps

502.6 mg (1.42 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol was initially charged in 8 ml of xylene (isomer mixture) and admixed with 96.6 mg (2.21 mmol) of sodium hydride (55 percent dispersion in mineral oil). After 1 hour, 340.8 mg (1.47 mmol) of chlorodiphenylphosphine in 2.5 ml of xylene was added at room temperature with vigorous stirring over a period of 5 min. The mixture was admixed with 34.6 mg (0.23 mmol) of sodium iodide and heated at 136° C. for 19 h. After 3 h, a further 25.1 mg of sodium iodide were added. After cooling to room temperature, the mixture was admixed with 30 ml of dilute sodium bisulfite solution and extracted with 50 ml of ethyl acetate. The organic phase was separated off and the aqueous phase was extracted with 50 ml of ethyl acetate. The combined organic phases were subsequently concentrated under reduced pressure. This gave 906 mg of crude product which was purified by silica gel chromatography (mobile phase: ethyl acetate), and 315.9 mg (41.3 percent) of N-[5-(diphenylphosphinoylmethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide was isolated in the form of a colorless solid.

Provenance & Evidence