Reaction Steps
A mixture of 3-((R)-3-((S)-1-(4′-fluorobiphenyl-4-yl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propanoic acid (500 mg, 1.12 mmol), HOBT (302 mg, 2.24 mmol), EDCl (440 mg, 2.24 mmol) and DIEA (1 mL) in anhydrous CH2Cl2 (10 mL) were stirred at 0□ under NH3. Then the solution was stirred at rt overnight. The solvent was removed under reduced pressure, and the residue was purified by preparative HPLC to afford 3-((R)-3-((S)-1-(4′-fluorobiphenyl-4-yl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propanamide (234 mg, yield 48%). 1H NMR (CDCl3): 1.49 (m, 3H), 1.91-2.02 (m, 1H), 1.87-1.98 (m, 1), 2.10-2.31 (m, 5H), 2.39-2.5 (m, 1H), 2.87 (m, 1H), 5.27 (s, 1H), 5.51 (s, 1H), 5.64 (m, 1H), 6.94 (m, 2H), 7.04 (m, 2H), 7.21-7.35 (m, 6H), 7.39 (m, 2H). LC-MS Method 3 tR=1.3, min, m/z=447, 469; 1H NMR (CDCl3) 1.49 (m, 3H), 1.91-2.02 (m, 1H), 1.87-1.98 (m, 1), 2.10-2.31 (m, 5H), 2.39-2.5 (m, 1H), 2.87 (m, 1H), 5.27 (s, 1H), 5.51 (s, 1H), 5.64 (m, 1H), 6.94 (m, 2H), 7.04 (m, 2H), 7.21-7.35 (m, 6H), 7.39 (m, 2H).
