反应详情

4-(4,5-Diamino-2′-trifluoromethyl-biphenyl-3-yl)-2-methyl-butan-2-ol (57.5 mg, 0.170 mmol, as prepared in the previous step) was placed in a 50 mL round-bottom flask equipped with a magnetic stir bar. DCM (15 mL), PyBrOP (95.0 mg, 0.204 mmol), and DIPEA (36.0 μL, 0.204 mmol) were added via syringe. 1-Oxa-2-aza-spiro[4.5]dec-2-ene-3-carboxylic acid (31.0 mg, 0.170 mmol, as prepared in Example 1, step B) in DCM (10 mL) was placed in an addition funnel and added dropwise over 2 h. After completion of the addition, the mixture was stirred at rt for 2 h. The solvent was removed under reduced pressure. The residue was chromatographed on a 40-g pre-packed SiO2 column eluting with EtOAc/heptane, 0:1 to 3:7, v/v over 20 min, yielding 34.4 mg (40%) of the title compound. Mass Spectrum (LCMS, ESI pos.) Calcd. for C27H32F3N3O3: 504.2 (M+H). Found 504.1.

1. customwas placed in a 50 mL round-bottom flask
2. customequipped with a magnetic stir bar
3. additionadded dropwise over 2 h
4. additionAfter completion of the addition
5. customThe solvent was removed under reduced pressure
6. customThe residue was chromatographed on a 40-g pre-packed SiO2 column
7. washeluting with EtOAc/heptane, 0:1 to 3:7, v/v over 20 min