Реакция #1861103

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

methylamine

methanol

cesium carbonate

→

methyl-[4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-8-yl]-amine

Растворители

dimethylformamide

Условия реакции

Обработка

1. 1
   ДругоеThe vial is evacuated
2. 2
   workup.ADDITIONfilled with argon
3. 3
   workup.ADDITIONWater and ammonia are 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 11% (B) to 21% (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) (276 mg, 0, 55 mmole) in dimethylformamide (5 mL) in a screw-capped vial are added a 3M solution of methylamine in methanol (2.8 mL, 5.5 mmoles), copper(I) iodide (100 mg, 0, 52 mmole) and cesium carbonate (250 mg, 0.77 mmole). The vial is evacuated and filled with argon. The reaction mixture is stirred at 100° C. for 36 hours. Water and ammonia are 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 11% (B) to 21% (B) in 10 minutes) to afford methyl-[4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-8-yl]-amine melting at 189° C.

Источник