反应详情

温度

80 °C

To a solution of 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 2A) (100 mg, 0.24 mmoles) in DMF (4 mL) in a screw-capped vial under argon are added methallyltributyltin (331 mg, 0.96 mmole), Pd(PPh3)4 (28 mg, 24 μmole), LiCl (51 mg, 1.2 mmoles). The reaction mixture is heated at 80° C. for 5 hours. A solution of 10% KF in water is added, and the aqueous phase is extracted three times with CH2Cl2. The organic phase is washed with a solution of 10% KF in water, brine, dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (98:2:0.2) to (96.5:3.5:0.35). As the residue is contaminated with tin salts, 1N aqueous HCl is added, and the aqueous phase is extracted three times with Et2O. The aqueous phase is basified to pH 10 with 12N NaOH and the aqueous phase is extracted three times with AcOEt. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure to afford 2-(2-methyl-allyl)-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene.

1. extractionthe aqueous phase is extracted three times with CH2Cl2
2. washThe organic phase is washed with a solution of 10% KF in water, brine
3. dry with materialdried over magnesium sulphate
4. filtrationfiltered
5. customthe solvent is removed under reduced pressure
6. customThe residue is purified by silica gel chromatography
7. additionis added
8. extractionthe aqueous phase is extracted three times with Et2O
9. extractionthe aqueous phase is extracted three times with AcOEt
10. dry with materialThe organic phase is dried over magnesium sulphate
11. filtrationfiltered
12. customthe solvent is removed under reduced pressure