Reaction Steps
To a solution of the title compound from Step E (0.058 g, 0.35 mmol) in DMF (1.68 mL) and water (0.06 mL) were added the title compound from Step C (0.076 g, 0.35 mmol) and OXONE® (0.139 g, 0.226 mmol). The resulting mixture was stirred at room temperature for 1 hour, then diluted with ethyl acetate and water. Solid potassium carbonate was added until the aqueous layer was basic (pH ˜9). Ethyl acetate was then added, and the organic layer was separated, washed with water and brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography on silica gel (10% acetone in dichloromethane, then 30% acetone in dichloromethane) provided the title compound as a racemic mixture. That racemic mixture was then separated into two enantiomers by HPLC (ChiralCel AS column, 25% MeOH (0.2% DEA)/CO2, 70 mL/min, 100 bar, 35° C.). Data for EXAMPLE 6 (Enantiomer A): LCMS m/z 365.99 [M+H]+; 1 H NMR (500 MHz, CDCl3) δ 9.14 (s, 1 H), 8.85 (s, 1 H), 8.59 (s, 1 H), 7.76 (dd, J=8.8, 4.8 Hz, 1 H), 7.30 (dd, J=8.5, 2.1 Hz, 1 H), 7.11-7.07 (m, 1 H), 4.85 (br s, 1 H), 3.55-3.53 (m, 1 H), 1.79 (s, 3 H), 1.22-1.12 (m, 2 H), 0.80-0.72 (m, 2 H). Data for Example 7 (Enantiomer B): LCMS m/z 365.97 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.16 (s, 1 H), 8.88 (s, 1 H), 8.57 (s, 1 H), 7.76 (dd, J=8.8, 4.8 Hz, 1 H), 7.30 (dd, J=8.5, 2.0 Hz, 1 H), 7.10-7.05 (m, 1 H), 3.91 (br s, 1 H), 3.56-3.55 (m, 1 H), 1.84 (s, 3 H), 1.18-1.15 (m, 2 H), 0.80-0.71 (m, 2 H).
