Tert-butoxycarbonylalanine → 2-((S)-1-tert-Butoxycarbonylaminoethyl)-3-cyclopropyl-5-fluoro-3H-benzoimidazole-4-carboxylic acid methyl ester

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Reaction Conditions

Reaction Steps

A mixture of 3-amino-2-cyclopropylamino-6-fluorobenzoic acid methyl ester (756 mg, 3.37 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (702 mg, 3.71 mmol), HOAt (505 mg, 3.71 mmol) and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (711 mg, 3.71 mmol) in DCM (20 mL) was stirred at 0° C. for 1 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic fraction was dried and concentrated in vacuo. The resulting residue was taken up in AcOH (20 mL) and heated at 70° C. for 21 h. After cooling to RT, the volatiles were evaporated in vacuo and the residue partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The aqueous phase was extracted with EtOAc and the combined organic fractions washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in DCM) to afford the title compound (700 mg, 55% over 2 steps). LCMS (Method C): RT 3.27 min [M+H]+ 378.18

Provenance & Evidence