Morpholine → (S)-1-(1-Methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a 100-mL three-neck round bottom flask equipped with an overhead stirrer, thermocouple, and condenser with gas inlet for nitrogen, was charged with KOt-Bu (95%, 8.3 g, 70.40 mmol, 4.0 eq) and 2-methyltetrahydrofuran (36 mL) followed by morpholine (18.5 mL, 210.6 mmol, 12.0 eq). The mixture was heated to 90-95° C. and then a solution of (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethan-1-amine (4.46 g, 210.6 mmol) in 2-methyltetrahydrofuran (9 mL) was added dropwise via a syringe pump over a period of one hour. Following addition of the amine, the transfer vessel was rinsed with 2-methyltetrahydrofuran (5 mL). The rinse was added to the reaction mixture, which was stirred at reflux for one hour. HPLC analysis indicated the reaction was complete. The slurry was then cooled to 60° C. and water (15 mL) was added, which dissolved the solids. The organic and aqueous phases were separated at 40-50° C. The aqueous phase was extracted with 2-methyltetrahydrofuran (20 mL) at 50° C. The organic layers were combined and concentrated under reduced pressure to afford crude product (9.0 g) which contained residual morpholine. The crude product was heated in hot toluene (30 mL). Some undissolved solids remained and the hot solution was decanted into a clean receiver. The toluene solution was cooled, resulting in crystallization of solids. The solution was further cooled in a refrigerator at 2-8° C. for one hour. The solids were filtered, washed with toluene (10 mL), and dried to afford the title compound as a tan solid (2.85 g).

Herkunft & Nachweise