反应详情

温度

110 °C

To a solution of compound 2-(4-bromophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 122A) (60 mg, 0.129 mmoles) in 1,4-dioxane (1.5 mL) in a screw-capped vial under argon are added diisopropylethylamine (33 μL, 0.142 mmole), 3-mercapto-3-methylbutan-1-ol (20 μL, 0.193 mmole), bis(dibenzilideneacetone)palladium(0) (4 mg, 6.4 μmole), Xantphos (4 mg, 6.4 μmole). The reaction mixture is heated at 110° C. overnight. As the reaction is not complete, bis(dibenzilideneacetone)Palladium(0) (4 mg, 6.4 μmole), Xantphos (4 mg, 6.4 μmole), diisopropylethylamine (33 μL, 0.142 mmole), 3-mercapto-3-methylbutan-1-ol (20 μL, 0.193 mmole) are added to the reaction mixture. After one overnight at 120° C., water is added to the reaction mixture and pH adjusted to 9-10 by adding concentrated ammonia 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 purified by silica gel chromatography using (CH2Cl2:MeOH) as eluent with a gradient from (95:5) to (90:10) to afford 3-methyl-3-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylsulfanyl}-butan-1-ol.

1. extractionThe aqueous phase is extracted three times with CH2Cl2
2. dry with materialThe organic phase is dried over magnesium sulphate
3. filtrationfiltered
4. customthe solvent is removed under reduced pressure
5. customThe residue is purified by silica gel chromatography