Bromine → Tert-butyl{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}carbamate

Potassium thiocyanate (2.70 g, 27.8 mmol) was dissolved in acetic acid (190 mL), tert-butyl{5-[(5-aminopyridin-2-yl)oxy]-4-chloro-2-fluorophenyl}carbamate (2.40 g, 6.78 mmol) was added, and the mixture was stirred at room temperature for 30 min. To the solution was added dropwise a solution (20 mL) of bromine (1.13 g, 7.07 mmol) in acetic acid, and the mixture was stirred at room temperature for 13 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (300 mL), and the solution was washed with saturated aqueous sodium hydrogen carbonate solution (100 mL×2) and saturated brine (50 mL), and dried over anhydrous magnesium sulfate. The dried organic layer was purified by basic silica gel chromatography (15 g, ethyl acetate), and the eluted fraction was concentrated under reduced pressure to give the title compound (2.69 g, 97%) as a white powder.

1. stirringthe mixture was stirred at room temperature for 13 hr
2. filtrationThe reaction mixture was filtered through celite
3. concentrationthe filtrate was concentrated under reduced pressure
4. dissolutionThe residue was dissolved in ethyl acetate (300 mL)
5. washthe solution was washed with saturated aqueous sodium hydrogen carbonate solution (100 mL×2) and saturated brine (50 mL)
6. dry with materialdried over anhydrous magnesium sulfate
7. customThe dried organic layer was purified by basic silica gel chromatography (15 g, ethyl acetate)
8. concentrationthe eluted fraction was concentrated under reduced pressure

ORD record

ord-3e4e4cb1f38a4dd9b25d96b170a087f9

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344135B2