反应详情

温度

80 °C

A vial containing the title compound from Example 61 Step B (15 mg, 0.05 mmol), the title compound from Example 22 Step B (11.7 mg, 0.047 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (3.68 mg, 5.19 μmol) and potassium carbonate (21.5 mg, 0.156 mmol) in tert-butanol (577 μL) and water (72 μL) 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 residue 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 M hydrochloric acid solution was added and the solution concentrated under reduced pressure to provide the title compound: LCMS m/z 414.79 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 9.38 (s, 1H), 9.11 (s, 1H), 8.85 (s, 1H), 8.27 (s, 1H), 7.92 (d, J=8.34 Hz, 1H) 7.87 (d, J=1.71 Hz, 1H), 7.81 (dd, J=1.94, 8.34 Hz, 1H), 3.15 (s, 4H).

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