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

To a solution of (S)-Boc-alaninamide (1.5 g, 7.9 mmol) in anhydrous THF (20 mL) was added triethyloxonium tetrafluoroborate (1.6 g, 8.3 mmol) in one portion under a nitrogen atmosphere. The resulting mixture was left to stir at RT for 2 h. The volatiles were removed in vacuo and the resulting residue redissolved in absolute EtOH (20 mL). To the mixture was added 4-fluoro-N2-pyridin-2-yl-benzene-1,2-diamine (1.0 g, 4.9 mmol) and the mixture stirred at 75° C. for 16 h. The volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with DCM and the combined organic fractions washed with water, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-40% EtOAc in cHex) to afford the title compound as an orange oil (1.6 g, 92%). LCMS (Method B): RT 3.21 min [M+H]+ 357.0.

1. waitThe resulting mixture was left
2. customThe volatiles were removed in vacuo
3. dissolutionthe resulting residue redissolved in absolute EtOH (20 mL)
4. stirringthe mixture stirred at 75° C. for 16 h
5. customThe volatiles were removed in vacuo
6. customthe resulting residue partitioned between DCM
7. extractionThe aqueous phase was further extracted with DCM
8. washthe combined organic fractions washed with water
9. dry with materialdried (MgSO4)
10. concentrationconcentrated in vacuo
11. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-40% EtOAc in cHex)

ORD record

ord-98ae5cd342524d4d96480a77e2044f3f

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2