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

Participants

Reaction Conditions

Reaction Steps

282.8 mg (0.80 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulphonylamino)pyrimidin-5-yl]methanol was initially charged in 4.5 ml of xylene (isomer mixture) and admixed with 55 mg (1.30 mmol) of sodium hydride (55 percent dispersion in mineral oil). After 35 min, 185 mg (0.84 mmol) of chlorodiphenylphosphine in 1.5 ml of xylene was added at room temperature with vigorous stirring over a period of 5 min, and the mixture was subsequently heated at 135° C. for 20 h. After cooling to room temperature, the mixture was admixed with 15 ml of water and extracted with 10 ml of ethyl acetate. The organic phase was separated off and the aqueous phase was extracted with 2×10 ml of ethyl acetate. The combined organic phases were subsequently dried (MgSO4) and concentrated under reduced pressure. This gave 510 mg of crude product which was purified by silica gel chromatography (mobile phase: n-hexane/ethyl acetate 1:2, then ethyl acetate), and 230 mg (53.5 percent) of N-[5-(diphenylphosphinoylmethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulphonamide was isolated in the form of a colorless solid.

Provenance & Evidence