Hydrogen Peroxide → HCID 68639349, compound

Participants

Reaction Steps

Di-tert-butyl diethylphosphoramidite (486 mg, 1.95 mmol) was added slowly to a solution of N-(2,3-difluorophenyl)-2-{4-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide (740 mg, 1.3 mmol) and tetrazole (228 mg, 3.25 mmol) in dimethylformamide (7.4 ml) under argon. The mixture was stirred at ambient temperature for 45 minutes. Hydrogen peroxide (9 N, 288 μl, 2.6 mmol) was added at 0° C. and the reaction stirred for 1.5 hours at ambient temperature. An additional quantity of hydrogen peroxide (72 μl, 0.65 mmol) was added to the solution to complete the oxidation. The mixture was cooled to 0° C. and a saturated solution of sodium metabisulphite (388 mg, 2 ml) was added slowly with vigorous stirring. The mixture was stirred at ambient temperature for 20 minutes, diluted with water and the pH adjusted to 7 with an aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (3×10 ml), dried and concentrated. Purification by silica gel chromatography, eluting with dichloromethane:methanol (98:2) followed by dichloromethane:methanolic ammonia (3 N) (9:1) yielded di-tert-butyl 2-[[3-({4-[(1-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl](propyl)amino]ethyl phosphate (720 mg, 67% yield):

Provenance & Evidence