Reacción #68644

Ecuación de reacción

potassium carbonate

3-(2-bromoethoxy)-8-chloro-1,5-naphthyridine

sodium iodide

(R)-3-fluoropyrrolidine hydrochloride

→

(R)-8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridine

Rendimiento 54.0%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroReaction mixture
2. 2
   Otroplaced in oil bath
3. 3
   Otropreheated to 60° C.
4. 4
   OtroReaction mixture
5. 5
   Lavadorinsed with 10% MeOH/DCM and filtrate
6. 6
   Concentraciónconcentrated
7. 7
   Otroto afford yellow oil
8. 8
   OtroThis was purified by ISCO silica gel chromatography (20-40% EtOAC/Hexanes)

Procedimiento

A 25 mL round bottom flask at rt was charged with (R)-3-fluoropyrrolidine hydrochloride (124 mg, 0.99 mmol). To this was added potassium carbonate (365 mg, 2.64 mmol), 3-(2-bromoethoxy)-8-chloro-1,5-naphthyridine (190 mg, 0.66 mmol), sodium iodide (149 mg, 0.99 mmol) and DMF (2 mL). Reaction mixture placed in oil bath preheated to 60° C. and allowed to stir for 16 hrs. Reaction mixture passed through celite cake, rinsed with 10% MeOH/DCM and filtrate concentrated to afford yellow oil. This was purified by ISCO silica gel chromatography (20-40% EtOAC/Hexanes) to afford (R)-8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridine (105 mg, 54% yield). MS [M+H]=296.2. Calc'd for C14H15ClFN3O=295.7.

Fuente