反应详情

温度

80 °C

To a vial containing the title compound from Example 22 Step B (0.020 g, 0.080 mmol), the title compound from Example 62 Step E (0.021 g, 0.080 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.132 mg, 1.599 μmol), and potassium carbonate (0.033 g, 0.240 mmol) were added tert-butanol (0.90 mL) and water (0.10 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 residue was diluted with acetonitrile and then 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 hydrochloric acid solution was added and the solution concentrated to provide the title compound: LCMS m/z 382.99 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 9.42 (s, 1H), 8.97 (s, 1H), 8.83 (s, 1H), 8.29 (s, 1H), 7.93-7.91 (m, 2H), 7.85-7.83 (m, 1H), 3.18-3.13 (m, 4H), 2.96 (q, J=7.43 Hz, 2H), 1.87 (s, 6H), 1.07 (t, J=7.43, 3H).

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 residue was diluted with acetonitrile
6. custompurified by HPLC (C18 column, 10 to 100% acetonitrile/water
7. additionFractions containing product
8. additionaqueous 1 N hydrochloric acid solution was added
9. concentrationthe solution concentrated