反应详情

温度

120 °C

To a solution of compound 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 2A) (50 mg, 0.12 mmoles) in 1,4-dioxane (500 μL) in a screw-capped vial under argon are added potassium vinyltrifluoroborate (21 mg, 0.156 mmole), Pd(OAc)2 (1.35 mg, 6 μmole), RuPhos (3 mg, 6 μmole), K2CO3 (50 mg, 0.36 mmole) and water (400 μL). The reaction mixture is heated to 120° C. for overnight. As the reaction is not complete, potassium vinyltrifluoroborate (21 mg, 0.156 mmole), Pd(OAc)2(1.35 mg, 6 μmole), RuPhos (3 mg, 6 μmole) are added and the reaction mixture is heated to 120° C. for 3 hours. Water is added, pH adjusted to 9-10 with saturated Na2CO3 solution. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (99:1:0.1) to (95:5:0.5) and the residue is submitted to a preparative thin-layer chromatography eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1) to afford 4-(1-methylpiperidin-4-yloxy)-2-vinyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene.

1. temperaturethe reaction mixture is heated to 120° C. for 3 hours
2. extractionThe aqueous phase is extracted three times with CH2Cl2
3. dry with materialThe organic phase is dried over magnesium sulphate
4. filtrationfiltered
5. customthe solvent is removed under reduced pressure
6. customThe residue is pre-purified by silica gel chromatography
7. washeluting with (CH2Cl2:MeOH:NH4OH) (9:1:1)