反应详情

温度

90 °C

To a stirred solution of Intermediate 223B (0.024 g, 0.136 mmol) in toluene (1 mL) was added TEA (0.076 mL, 0.543 mmol), DPPA (0.074 mL, 0.339 mmol) and the reaction mixture was heated to 90° C. for 2 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (0.040 g, 0.136 mmol) in THF (0.5 mL) and stirred for 12 h. The reaction mixture was quenched with a 10% aqueous solution of NaHCO3 and extracted with EtOAc (3×10 mL) The combined organic layer was washed with water, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by preparative HPLC to afford Compound 223 as an off-white solid (10 mg, 15%). HPLC retention times 2.35 min. and 2.35 min (Method E and L respectively). MS(ES): m/z=472 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (dd, J=7.28, 2.26 Hz, 1H), 7.66-7.71 (m, 1H), 7.42-7.48 (m, 1H), 7.30-7.37 (m, 7.11-7.22 (m, 1H), 6.99 (s, 1H), 6.47-6.87 (m, 1H), 4.72 (s, 2H), 4.09-4.14 (t, J=5.52 Hz, 2H), 4.04 (s, 2H), 3.84 (t, J=5.52 Hz, 2H), 2.04-2.15 (m, 4H), 1.80 (d, J=9.04 Hz, 2H).

1. temperatureThe reaction mixture was cooled to RT and to it
2. customThe reaction mixture was quenched with a 10% aqueous solution of NaHCO3
3. extractionextracted with EtOAc (3×10 mL) The combined organic layer
4. washwas washed with water
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationthe filtrate concentrated
8. customThe crude product was purified by preparative HPLC