反应详情

温度

90 °C

A solution of N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide (100 mg, 301 μmol) produced in Example D17(iv), 2-chloro-3-(1-cyanocyclopropyl)benzoic acid (167 mg, 753 μmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (286 mg, 753 μmol) in pyridine (4 mL) was stirred at 90° C. for 3 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 silica gel column chromatography (hexane/ethyl acetate=40/60→20/80), 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 (79 mg, 49%) as colorless crystals.

1. extractionthe mixture was extracted with ethyl acetate (20 mL, 5 mL)
2. washThe combined organic layer was washed with saturated brine (5 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationThe insoluble material was filtered off
5. concentrationthe filtrate was concentrated under reduced pressure
6. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=20/80→0/100) and silica gel column chromatography (hexane/ethyl acetate=40/60→20/80)
7. additionthe fractions containing the object product
8. concentrationwere concentrated under reduced pressure
9. customThe obtained residue was recrystallized from ethyl acetate