Реакция #1861100

Уравнение реакции

8-bromo-4-(1-methyl-piperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

8-Bromo-4-(1-methyl-piperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

benzylboronic pinacol ester

potassium carbonate

→

8-benzyl-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

Растворители

toluene dioxane water

Условия реакции

Обработка

1. 1
   ДругоеThe vial is evacuated
2. 2
   workup.ADDITIONfilled with argon
3. 3
   workup.ADDITIONWater is added to the reaction mixture
4. 4
   Экстракцияthe aqueous phase is extracted three times with dichloromethane
5. 5
   СушкаPooled organic extracts are dried over magnesium sulphate
6. 6
   Фильтрацияfiltered
7. 7
   Другоеthe solvent is removed under reduced pressure
8. 8
   ДругоеThe 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)

Методика

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) (150 mg) in toluene/dioxane/water 10/1/1 (6 mL) in a screw-capped vial are added benzylboronic pinacol ester (151 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (50 mg) and potassium carbonate (137 mg). The vial is evacuated and filled with argon. The reaction mixture is stirred at 95° C. for 20 hours. Water is added to the reaction mixture, and the aqueous phase is extracted three times with dichloromethane. Pooled organic extracts are dried over magnesium sulphate, filtered and the solvent is 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 8-benzyl-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene melting at 66° C.

Источник