反应详情

温度

70 °C

A stirred solution of 3,3-difluoro-2,2-dimethylpropanoic acid (28.1 mg, 0.204 mmol) in toluene (2 mL) at RT was added TEA (0.043 mL, 0.305 mmol) and DPPA (0.047 mL, 0.204 mmol) and the solution was stirred at 70° C. for 2 h. The reaction mixture was cooled to RT, to which was added Intermediate 185B (30 mg, 0.102 mmol) in THF (1 mL) and stirred for 12 h. The reaction mass was diluted with ethyl acetate (5 mL), the organic layer was separated, washed with 10% aqueous NaHCO3, water, brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude compound was purified by preparative HPLC to afford Compound 185 as pale yellow solid (37 mg, 84% yield). The HPLC retention times are 2.020 min and 2.030 min (Methods J and K respectively); MS(ES): m/z=430.2[M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.79-7.90 (m, 1H), 7.63-7.76 (m, 1H), 7.41-7.52 (m, 1H), 7.2-7.4 (m, 2H) 6.66-6.74 (m, 1H), 6.24-6.62 (m, 1H), 4.64-4.79 (m, 2H), 4.06-4.17 (m, 2H), 3.78-3.91 (m, 2H), 1.25 (s, 6H).

1. temperatureThe reaction mixture was cooled to RT, to which
2. stirringstirred for 12 h
3. customthe organic layer was separated
4. washwashed with 10% aqueous NaHCO3, water, brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationthe filtrate concentrated
8. customThe crude compound was purified by preparative HPLC