反应详情

温度

95 °C

To a solution of 8-bromo-4-(1-methyl-piperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 231) (276 mg, 0, 61 mmole) in anhydrous dimethylformamide (5 mL) in a screw-capped vial are added n-tetrabutylammonium bromide (196 mg, 0, 61 mmole), lithium chloride (26 mg, 0, 61 mmole), palladium(II) acetate (27 mg, 0, 12 mmole), styrene (174 μL, 1, 5 mmole) and potassium carbonate (420 mg, 3, 0 mmoles). The vial is evacuated and filled with argon. The reaction mixture is stirred at 95° C. for 20 hours. Water and diethyl ether are added to the reaction mixture. The organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated under reduced pressure. To the residue are added methanol (10 mL), 10% Pd/C (150 mg) and ammonium formate (3 g). After reflux for 1.5 hours the mixture is filtered on a celite pad, concentrated under reduced pressure, diluted with ethyl acetate, washed with water, dried over magnesium sulphate and the solvent was removed under reduced pressure. The residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 23% (B) to 33% (B) in 10 minutes) to afford 4-(1-methyl-piperidin-4-yloxy)-8-phenethyl-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene melting at 67° C.

1. customThe vial is evacuated
2. additionfilled with argon
3. additionWater and diethyl ether are added to the reaction mixture
4. washThe organic phase is washed with water
5. dry with materialdried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. additionTo the residue are added methanol (10 mL), 10% Pd/C (150 mg) and ammonium formate (3 g)
9. temperatureAfter reflux for 1.5 hours the mixture
10. filtrationis filtered on a celite pad
11. concentrationconcentrated under reduced pressure
12. additiondiluted with ethyl acetate
13. washwashed with water
14. dry with materialdried over magnesium sulphate
15. customthe solvent was removed under reduced pressure
16. customThe residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 23% (B) to 33% (B) in 10 minutes)