Diethyl chlorophosphate → 5-cyano-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo [2,3-b]pyridin-3-yl)pyrimidin-2-yl diethyl phosphate

Participants

Reaction Conditions

Reaction Steps

2-hydroxy-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (87% pure, 1.23 g, 2.329 mmol) in dry THF (24.60 mL) was stirred at −25° C. and treated with potassium t-butoxide (2.795 mL of 1.0 M, 2.795 mmol) in THF. The reaction mixture was warmed up to 0° C. for 20 minutes, cooled to −50° C. and treated with diethylchlorophosphate (482.3 mg, 403.9 μL, 2.795 mmol). The reaction mixture was stirred at −40° C. for 20 minutes and at room temperature for 2 hours. The reaction mixture was diluted with ice cold ethyl acetate (60 mL), cooled in ice and shaken quickly with ice cold water containing 1M HCl (2.8 mL, 2.8 mmol), basified with aqueous NaHCO3 and extracted into ethyl acetate. The organic extracts were dried over magnesium sulfate and concentrated to give a pale yellow solid which was triturated with ether and filtered to give a pale yellow solid (810 mg). The mother liquors were concentrated in vacuo and the residue purified on silica gel by flash column chromatography to afford a colourless solid (219 mg) (total: 1.029 g, 74% yield).

Provenance & Evidence