反应详情

The product of Example 444A (93 mg.) was reacted with trifluoroacetic acid [TFA] (0.60 mL) in dichloromethane (0.60 mL) added dropwise at room temperature then stirred at room temperature for 1 hour. The reaction mixture was concentrated and partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was washed with brine, dried over MgSO4, and concentrated. The residue was chromatographed on a C-18 HPLC column with a gradient elution of acetonitrile in 0.1% TFA water (0-100%). The desired fractions were combined, concentrated, dissolved in ethyl acetate, washed with saturated aqueous NaHCO3 then brine, dried over MgSO4 and concentrated to give a pale yellow amorphous solid (67 mg, 84%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.07 (t, J=6.99 Hz, 3 H) 1.34 (d, J=6.62 Hz, 6 H) 1.84 (s, 3 H) 3.15-3.29 (m, 1 H) 4.03 (q, J=7.35 Hz, 2 H) 5.59 (s, 2 H) 6.62 (d, J=8.46 Hz, 2 H) 6.84 (d, J=8.46 Hz, 1 H) 7.12 (d, J=8.46 Hz, 2 H) 7.24-7.41 (m, 4 H) 7.52 (d, J=7.35 Hz, 2 H) 7.63 (d, J=8.46 Hz, 1 H) 7.73 (dd, J=8.46, 1.84 Hz, 1 H) 7.90 (d, J=1.84 Hz, 1 H) 8.57 (s, 1 H) 8.83 (s, 1 H) 8.86 (d, J=8.46 Hz, 2 H) 10.13 (s, 1 H).

1. additionadded dropwise at room temperature
2. concentrationThe reaction mixture was concentrated
3. custompartitioned between ethyl acetate and saturated aqueous NaHCO3
4. washThe organic layer was washed with brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated
7. customThe residue was chromatographed on a C-18 HPLC column with a gradient elution of acetonitrile in 0.1% TFA water (0-100%)
8. concentrationconcentrated
9. dissolutiondissolved in ethyl acetate
10. washwashed with saturated aqueous NaHCO3
11. dry with materialbrine, dried over MgSO4
12. concentrationconcentrated