Pyridine → HCID 117872741, compound

Participants

Reaction Conditions

Reaction Steps

Cyanuric fluoride (3.25 g, 2.08 mL, 24.1 mmol) was added to a solution of (S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyric acid (5.4 g, 17.9 mmol) and pyridine (1.95 mL, 24.1 mmol) in CH2Cl2 (100 mL). The reaction mixture was stirred at 23° C. for 2.5 h. The resulting precipitate was filtered off and the mother liquor was concentrated. The residue was dissolved in EtOAc (250 mL), and the solution was washed with saturated NaHCO3, 0.5 M citric acid and brine. The organic layer was dried over Na2SO4, filtered, concentrated and dried under vacuum. The resulting yellow oil was taken up in CH2Cl2 (35 mL) and cooled in a dry ice-MeOH bath. To this solution was added a solution of (S)-ethyl indoline-2-carboxylate (2.3 g, 12.0 mmol) and 2,6-di-tert-butylpyridine (4.6 g, 5.31 mL, 24.1 mmol) in 25 mL of CH2Cl2. The resulting mixture was stirred at rt overnight. The crude material was purified by flash chromatography (silica gel, 0% to 70% EtOAc in hexanes) to give (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-indole-2-carboxylic acid ethyl ester (2.93 g), m/z=476 (M+H).

Provenance & Evidence