Sodium Bicarbonate → N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl]amino}-4-chloro-2-fluorophenyl)-3-(1,1-dimethylprop-2-yn-1-yl)benzamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-{5-[(5-amino-2-chloro-4-fluorophenyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide (78 mg, 221 μmol) produced in Example D46(iii), 3-(1,1-dimethylprop-2-yn-1-yl)benzoic acid (79 mg, 442 μmol) produced in Example D20(iii) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (168 mg, 442 μmol) in pyridine (3 mL) was stirred at 90° C. for 5 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (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 and hexane to give the title compound (89 mg, 77%) as colorless crystals.

Provenance & Evidence