Triethylamine → Ethyl 4'-[(1R)-1-[[(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetyl](methyl)amino]-2-(4-morpholinyl)ethyl]-4-biphenylcarboxylate

Participants

Reaction Steps

Ethyl 4′-[(1R)-1-(methylamino)-2-(4-morpholinyl)ethyl]-4-biphenylcarboxylate (59.7 mg, 0.16 mmol) was dissolved in 10 mL of DMF at room temperature with magnetic stirring. The resulting solution was treated with (6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid (63.8 mg, 0.18 mmol, with 23 wt % LiCl) followed by triethylamine (32.4 mg, 0.32 mmol) and BOP (78.7 mg, 0.18 mmol), and then the reaction mixture was maintained at room temperature for 16 h. The reaction mixture was concentrated and the residue was partitioned between EtOAc and saturated aqueous NaHCO3 solution. The organic layer was washed by brine, dried over MgSO4, filtered and then concentrated. The residue was dissolved in 2 mL of DMSO and purified by preparative HPLC (Xterra Prep RP, 30×100 mm, 25 mL/min, A: acetonitrile with 0.1% TFA, B: water with 0.1% TFA, A: 15% to 90% during 20 min, UV detection at 214 nm) to give 44 mg (37% yield) of the title compound as a yellow solid. MS (ES) m/e 626 [M+H]+.

Provenance & Evidence