Triethyloxonium tetrafluoroborate → (S)-1-[6-Fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]ethylamine

To a suspension of (S)-Boc-alaninamide (337 mg, 1.79 mmol) in DCM (5 mL) was added triethyloxonium tetrafluoroborate (340 mg, 1.79 mmol) in one portion under a nitrogen atmosphere. The resulting mixture was left to stir at RT for 1 h. The volatiles were removed under reduced pressure and to the resulting residue was added 4-fluoro-N2-(5-fluoropyridin-3-yl)-benzene-1,2-diamine (198 mg, 0.895 mmol) in absolute EtOH (5 mL) and the mixture stirred at 80° C. for 18 h. The volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic fraction was dried, concentrated in vacuo and the resulting residue taken up in DCM (2 mL) and TFA (1 mL) added. After stirring at RT for 1 h, the reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-20% MeOH in DCM) to afford the title compound as a colourless oil (52 mg, 21% over 2 steps). LCMS (Method C): RT 1.76 min [M+H]+ 275.20

1. waitThe resulting mixture was left
2. customThe volatiles were removed under reduced pressure and to the resulting residue
3. stirringthe mixture stirred at 80° C. for 18 h
4. customThe volatiles were removed in vacuo
5. customthe resulting residue partitioned between DCM
6. customThe organic fraction was dried
7. concentrationconcentrated in vacuo
8. additionTFA (1 mL) added
9. stirringAfter stirring at RT for 1 h
10. additionthe reaction mixture was diluted with MeOH
11. washThe cartridge was washed with MeOH
12. concentrationconcentrated in vacuo
13. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-20% MeOH in DCM)

ORD record

ord-e0999ee2f432483a8c58ca497f88997f

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2