Trifluoroacetic acid → HCID 57418644, compound

Participants

Reaction Steps

1-(4-biphenylyl)-N-methyl-2-(4-morpholinyl)ethanamine (0.68 g, 2.3 mmol) and {6-[(ethyloxy)carbonyl]-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl} acetic acid (0.8 g, 2.5 mmol) were dissolved in 12 mL of methylene chloride. Triethylamine (1.3 mL, 9.2 mmol) was delivered to the room temperature mixture, and the solution was allowed to stir for several minutes before a separate solution of 1H-1,2,3-benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 1.11 g, 2.5 mmol) dissolved in 5 mL of methylene chloride was added to the mixture at room temperature. The reaction was maintained at that temperature for 18 hours, before it was determined to be complete by LCMS (two Aquasil C18, 20×1 mm columns were run in sequence, 4 minutes at 0.1 mL/min, 1-99% CH3CN/H2O with 0.018% trifluoroacetic acid, ES) Rt=2.7 min and m/e 558 [M+1]+. Solvent was removed by rotary evaporation and the crude residue was purified by prep HPLC (Waters, 50×100 mm, 84 mL/min, A: acetonitrile B: water (pH=10, NH4OH), A: 10 to 99% over 15 min, UV detection at 214 nm) to give the title compound (0.58 g. 1.0 mmol, 43%) as an off-white amorphous solid. MS (ES) m/e 558 [M+H]+.

Provenance & Evidence