Dimethylformamide → 3-(1-cyano-1-methylethyl)-N-{3-[(2-{[(4,4-difluoropiperidin-1-yl)acetyl]amino}[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]-4-methylphenyl}benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-[3-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl}amino)-4-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide (150 mg, 288 μmol) produced in Example D32(i) in tetrahydrofuran (4 mL)/N,N-dimethylformamide (0.5 mL) were added triethylamine (180 μL, 1.30 mmol) and 4,4-difluoropiperidine hydrochloride (68 mg, 432 μmol), and the mixture was stirred at 60° C. for 7 hr. To the reaction mixture was added water (15 mL), and the mixture was extracted with ethyl acetate (20 mL, 5 mL). The combined organic layer was washed with saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=20/80→0/100), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate to give the title compound (82 mg, 47%) as colorless crystals.

Provenance & Evidence