反应详情

温度

80 °C

To a vial containing the title compound from Example 22 Step B (0.025 g, 0.100 mmol), the title compound from Example 72 Step C (0.027 g, 0.100 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.4 mg, 2.0 μmol), and potassium carbonate (0.041 g, 0.300 mmol) were added tert-butanol (1.1 mL) and water (0.14 mL). The vial was flushed with nitrogen, sealed tightly and heated to 80° C. overnight. The reaction solution was then cooled to room temperature and concentrated under reduced pressure. The resulting material was diluted with acetonitrile and purified by HPLC (C18 column, 10 to 100% acetonitrile/water, both 0.1% v/v trifluoroacetic acid). Fractions containing product were combined, aqueous 1 N HCl solution was added, and the resulting solution concentrated under reduced pressure to provide the title compound: LCMS m/z 397.02 [M+H]+; 1H NMR (500 MHz, CD3OD) δ 9.37 (s, 1H), 9.01 (s, 1H), 8.85 (s, 1H), 8.60 (s, 1H), 7.92-7.86 (m, 3H), 3.27-3.24 (m, 4H), 2.02-1.99 (m, 1H), 1.92-1.90 (m, 2H), 1.78-1.76 (m, 2H), 1.04-1.00 (m, 2H), 0.91-0.89 (m, 2H).

1. customThe vial was flushed with nitrogen
2. customsealed tightly
3. temperatureThe reaction solution was then cooled to room temperature
4. concentrationconcentrated under reduced pressure
5. additionThe resulting material was diluted with acetonitrile
6. custompurified by HPLC (C18 column, 10 to 100% acetonitrile/water
7. additionFractions containing product
8. additionaqueous 1 N HCl solution was added
9. concentrationthe resulting solution concentrated under reduced pressure