Ethyl Acetate → HCID 22950007, compound

Participants

Reaction Conditions

Reaction Steps

N-[(Dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridin-1-ylmethylene]-N-methylmethaninium hexafluorophosphate N-oxide (740 mg, 1.95 mmol) was added to a stirred solution of (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-(3-fluoro-4-phenoxyphenyl)hexanoic acid (Preparation 5) (731 mg, 1.30 mmol) and diisopropylethylamine (220 μL, 1.30 mmol) in anhydrous dimethylformamide (10 mL) at 0° C. under nitrogen. After 25 min, hydroxylamine hydrochloride (271 mg, 3.90 mmol) was added followed by diisopropylethylamine (880 μL, 5.20 mmol). The resulting mixture was stirred at 20° C. for 16 h, poured into ethyl acetate (150 mL) and washed with pH 7 phosphate buffer solution (3×50 mL), saturated aqueous sodium chloride (50 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was recrystallised from dichloromethane/diisopropyl ether to give the title compound as a colourless solid (275 mg, 24%). Further purification of a sample (130 mg) by preparative hplc (Phenomenex C18 Magellan column, 150×20 mm, 5μ packing, 20 mL/min acetonitrile:aqueous phosphate buffer (8.3 mM, pH 7.2)=1:1, retention time 13.5 min), then trituration with diisopropyl ether, filtration and drying in vacuo at 50° C. gave 50 mg of a white solid.

Provenance & Evidence