Triethylamine → [(S)-1-(3-Cyano-4-fluoro-2-phenylaminophenylcarbamoyl)propyl]carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Triethylamine (0.55 mL, 3.96 mmol) was added to a stirred mixture of 3-amino-6-fluoro-2-phenylaminobenzonitrile (0.30 g, 1.32 mmol), (S)-(2-tert-butoxycarbonylamino)butyric acid (0.30 g, 1.45 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.28 g, 1.45 mmol) and HOAt (0.20 g, 1.45 mmol) in DCM at 0° C. under nitrogen. The resultant mixture was stirred at 0° C. for 5 minutes then 20° C. for 16 h. The reaction mixture was re-cooled to 0° C. and (S)-2-tert-butoxycarbonylaminobutyric acid (0.30 g, 1.45 mmol), N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide hydrochloride (0.28 g, 1.45 mmol), HOAt (0.20 g, 1.45 mmol) and triethylamine (0.55 mL, 3.96 mmol) added sequentially, and the resultant mixture stirred at 20° C. for 24 h. The mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and DCM (3×20 mL). The combined DCM extracts were washed with water, dried (Na2SO4) and concentrated in vacuo to give the title compound as an off white foam (0.64 g). LCMS (method H): Rt 2.93 min, [M+H]+ 413.

Provenance & Evidence