反应详情

[7-(methyloxy)-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetic acid, lithium salt (106 mg, 0.44 mmol), [1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]methylamine (122 mg, 0.44 mmol), triethylamine (91 uL, 0.66 mmol), and (1H-1,2,3-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (BOP Reagent, 232 mg, 0.524 mmol) were added in that order to a 4 mL screw capped vial that contained 1 mL of anhydrous DMF. The reaction mixture was stirred for 20 hours at room temperature, after which time HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) showed that the reaction was complete. The solvent was removed under vacuum and the residue was dissolved in 2 mL of DMSO, filtered through a 0.2 um PTFE Acrodisk, and purified by reverse-phase HPLC (Phenomenex C-18, 50×100 mm, 80 mL/min, A: acetonitrile (0.1% TFA) B: water (0.1% TFA), A: 15 to 98% over 20 min, UV detection at 214 nm) to give the title compound (123 mg, 0.246 mmol, 56%) as the TFA salt in the form of an off-white solid. MS (ES) m/e 501 [M+H]+.

1. customcapped vial
2. customThe solvent was removed under vacuum
3. dissolutionthe residue was dissolved in 2 mL of DMSO
4. filtrationfiltered through a 0.2 um PTFE Acrodisk
5. custompurified by reverse-phase HPLC (Phenomenex C-18, 50×100 mm, 80 mL/min
6. waitA: acetonitrile (0.1% TFA) B: water (0.1% TFA), A: 15 to 98% over 20 min