Triethyloxonium tetrafluoroborate → [(S)-1-(7-Bromo-6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

To a suspension of ((S)-1-carbamoylethyl)carbamic acid tert-butyl ester (1.0 g, 5.4 mmol) in DCM (10 mL) was added triethyloxonium tetrafluoroborate (1.1 g, 5.78 mmol) and the reaction mixture stirred at RT for 2 h, during which the solids dissolved. The reaction mixture was concentrated in vacuo and the residue dissolved in ethanol (10 mL). 3-Bromo-4-fluoro-N2-pyridin-2-yl-benzene-1,2-diamine (0.96 g, 3.4 mmol) was added and the reaction heated at 75° C. for 16 h. The reaction mixture was concentrated in vacuo, the residue dissolved in water and the product extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane) to yield the title compound as a white solid (832 mg, 56%). LCMS (Method C): RT=3.39 min, [M+H]+=435+437.

1. dissolutiondissolved
2. concentrationThe reaction mixture was concentrated in vacuo
3. dissolutionthe residue dissolved in ethanol (10 mL)
4. temperaturethe reaction heated at 75° C. for 16 h
5. concentrationThe reaction mixture was concentrated in vacuo
6. dissolutionthe residue dissolved in water
7. extractionthe product extracted with EtOAc (3×20 mL)
8. washThe combined organic extracts were washed with brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated in vacuo
11. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane)

ORD record

ord-fede5675c9384efdbeaf35d4a3af279a

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2