反应详情

温度

70 °C

To a stirred solution of Intermediate 229D (16.71 mg, 0.102 mmol) in toluene (1 mL) at RT under nitrogen was added TEA (0.043 mL, 0.305 mmol), DPPA (0.047 mL, 0.204 mmol) and the reaction mixture was heated at 70° C. for 2 h. The reaction mass was cooled to RT and to it was added a solution of Intermediate 185B (30 mg, 0.102 mmol) in THF (1 mL) and stirred at RT for 16 h. The reaction mass was diluted with ethyl acetate (5 mL), the organic layer was separated, washed successively with an aqueous solution of NaHCO3, water, brine, then dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude product was purified by preparative HPLC to afford Compound 229 as a pale yellow solid (2 mg, 4%). The HPLC retention times are 1.484 min. and 1.500 min. (Methods E and L respectively); MS(ES): m/z=456.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (dd, J=7.31, 2.16 Hz, 1H), 7.68 (ddd, J=8.67, 4.78, 2.16 Hz, 1H), 7.42 (m, 1H), 7.36 (bs, 1H), 7.18 (bs, 1H), 7.11 (s, 1H), 4.76 (s, 2H), 4.14 (t, J=5.30 Hz, 2H), 3.86 (t, J=5.33 Hz, 2H), 3.17 (d, J=5.90 Hz, 2H), 2.55-2.70 (m, 2H), 2.17 (d, J=9.79 Hz, 2H), 1.15 (s, 3H).

1. temperatureThe reaction mass was cooled to RT and to it
2. customthe organic layer was separated
3. washwashed successively with an aqueous solution of NaHCO3, water, brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate concentrated under reduced pressure
7. customThe crude product was purified by preparative HPLC