反应详情

A solution of Example 294 (0.0590 g, 0.17 mmol) in CH2Cl2 (3.0 mL) was treated with chloroacetyl chloride (16 μL, 0.20 mmol) and pyridine (69 μL, 0.85 mmol), stirred 4 hours at room temperature, then quenched with 1N HCl (10 mL). The layers were separated and the organic layer was washed with brine, dried (MgSO4), filtered, and concentrated to a residue (45.0 mg). The residue was dissolved in acetone (0.4 mL), treated with diethylamine (50 μL, 0.48 mmol), heated to 60° C. for 2 hours, cooled to room temperature, diluted with ethyl acetate (10 mL), and washed with 1N HCl (10 mL). The organic layer was dried (MgSO4), filtered and concentrated. The concentrate was purified by C18 reverse-phase HPLC using acetonitrile/water/0.1% TFA to provide the desired product (8.7 mg, 18%). MS (ESI(+)) m/e 460 (M+H)+; MS (ESI(−)) m/e 458 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 7.79 (m, 2H), 7.56 (m, 1H), 7.23 (m, 2H), 6.90 (m, 1H), 3.30 (m, 4H), 2.80 (m, 2H), 2.73 (s, 2H), 2.59 (m, 2H), 1.61 (m, 4H), 1.06 (m, 6H).

1. customquenched with 1N HCl (10 mL)
2. customThe layers were separated
3. washthe organic layer was washed with brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated to a residue (45.0 mg)
7. dissolutionThe residue was dissolved in acetone (0.4 mL)
8. temperatureheated to 60° C. for 2 hours
9. temperaturecooled to room temperature
10. washwashed with 1N HCl (10 mL)
11. dry with materialThe organic layer was dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customThe concentrate was purified by C18 reverse-phase