反应详情

温度

80 °C

To a solution of Intermediate 232C (56.0 mg, 0.271 mmol) in toluene (2 mL) was added TEA (0.057 mL, 0.407 mmol), DPPA (0.078 mL, 0.339 mmol) and the reaction mixture heated to 80° C. and stirred for 2 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (40 mg, 0.136 mmol) in THF (1 mL) and stirred for 12 h. The reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (2×20 mL) The combined organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude compound was purified by reverse phase preparative HPLC to afford Compound 232 (37 mg, 52%). HPLC retention time 1.70 min. and 1.70 min. (Methods J and K respectively). MS(ES): m/z=498 [M+H]+; 1H NMR (400 MHz, DMSO-d6) ppm 7.85 (dd, J=7.3, 2.3 Hz, 1H), 7.73-7.65 (m, 1H), 7.50-7.43 (m, 1H), 7.35 (br. s., 1H), 7.20 (br. s., 1H), 6.21 (s, 1H), 4.69 (s, 2H), 4.12 (t, J=5.0 Hz, 2H), 3.80 (t, J=5.3 Hz, 2H), 2.20 (t, J=12.0 Hz, 1H), 2.08-1.95 (m, 2H), 1.81-1.58 (m, 4H), 1.30-1.13 (m, 8H).

1. temperatureThe reaction mixture was cooled to RT and to it
2. stirringstirred for 12 h
3. extractionextracted with ethyl acetate (2×20 mL) The combined organic layer
4. washwas washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationthe filtrate concentrated
8. customThe crude compound was purified by reverse phase preparative HPLC