Ethyl Acetate → 2-{(3S)-7-Chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetamide

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Reaction Steps

PyBOP (127 mg, 0.24 mmol) and TEA (0.141 mL, 1.02 mmol) was added to a solution of {(3S)-7-chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetic acid (Intermediate 22a, 82 mg, 0.20 mmol) in DCM (2 mL). Thereafter, NH4Cl (43.6 mg, 0.81 mmol) was added and the mixture was stirred at rt for 1.5 h. EtOAc (30 mL) was added and the mixture was washed with sat. aq. Na2CO3 (30 mL), HCl (0.5M, 20 mL) and brine (20 mL). The product was purified by preparative HPLC (Phenomenex Luna Hilic column (5 μm 250×30 ID mm) using a gradient of 10 to 45% MeOH/DEA 100/0.5 in CO2, 120 bar, over 6 min at 40 OC) to give the title compound (42.0 mg, 51.3%).

Provenance & Evidence