Methanol → N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide

To a suspension of sodium borohydride (3.34 g, 88.2 mmol) in ethanol (40 mL) were added methanol (1 mL) and N-{5-[{4-fluoro-3-[(trifluoroacetyl)amino]phenyl}(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (1.71 g, 3.77 mmol) at 4° C., and the mixture was stirred for 30 min. The reaction mixture was poured into a two-layer solvent of ethyl acetate (200 mL) and 5% aqueous ammonium chloride solution (200 mL), and the mixture was vigorously stirred at room temperature for 5 min. The aqueous layer was separated, and extracted with ethyl acetate (200 mL). The combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (200 mL) and saturated brine (200 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→60/40), and the obtained solution was concentrated under reduced pressure to give the title compound (1.19 g, 88%) as a colorless powder.

1. stirringthe mixture was vigorously stirred at room temperature for 5 min
2. customThe aqueous layer was separated
3. extractionextracted with ethyl acetate (200 mL)
4. washThe combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution (200 mL) and saturated brine (200 mL)
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationThe insoluble material was filtered off
7. concentrationthe filtrate was concentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→60/40)
9. concentrationthe obtained solution was concentrated under reduced pressure

ORD record

ord-5fde38b0edb44a948e3cc1a9d3fb5176

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344135B2