Triethyloxonium tetrafluoroborate → {(S)-1-[6-Fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl ester

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Reaction Steps

To a suspension of (S)-Boc-alaninamide (17.4 g, 92.5 mmol) in DCM (180 mL, dried over molecular sieves) was added triethyloxonium tetrafluoroborate (16.0 g, 84.1 mmol) in one portion under a nitrogen atmosphere. The resulting mixture was stirred at RT for 2 h. The volatiles were removed in vacuo and the resulting residue taken up in absolute EtOH (200 mL) then 4-fluoro-N2-(5-fluoropyridin-3-yl)-benzene-1,2-diamine (6.20 g, 28.0 mmol) added. After stirring the reaction mixture at 60° C. for 2 h, the solvent was removed in vacuo and the resulting residue partitioned between DCM and an aqueous solution of NaHCO3. The layers were separated and the aqueous fraction extracted with DCM. The combined organic fractions were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (120 g Si—PCC, gradient 0-70% EtOAc in DCM) to afford the title compound as a green solid (10.1 g, 96%). LCMS (Method C): RT 3.23 min [M+H]+ 375.18.

Provenance & Evidence