Reacción #162614

Ecuación de reacción

8-(6-chloro-2-(4-nitrophenyl)pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane

8-(6-Chloro-2-(4-nitrophenyl)pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane

3-Oxa-8-azabicyclo[3.2.1]octane hydrochloride

3-oxa-8-azabicyclo[3.2.1]octane hydrochloride

potassium carbonate

DIPEA

→

title compound

Rendimiento 45.9%

8,8′-(2-(4-Nitrophenyl)pyrimidine-4,6-diyl)bis(3-oxa-8-azabicyclo[3.2.1]octane)

Rendimiento 45.9%

Disolventes

dichloromethane

dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto give a yellow suspension
2. 2
   Lavadowashed
3. 3
   SecadoThe organic phase was dried over MgSO4
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated
6. 6
   workup.ADDITIONThe crude product was added to a silica gel column
7. 7
   Lavadowas eluted with ethyl acetate in hexanes (10-40%)

Procedimiento

In a 2-5 mL microwave vial was placed 8-(6-chloro-2-(4-nitrophenyl)pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane (36, 214 mg, 0.617 mmol) in dioxane (4 ml) to give a yellow suspension. 3-Oxa-8-azabicyclo[3.2.1]octane hydrochloride (33, 277 mg, 1.851 mmol), potassium carbonate (341 mg, 2.469 mmol) and DIPEA (0.647 ml, 3.70 mmol) were added. The reaction was heated under microwave irradiation at 220° C. for 1 h. The reaction mixture was diluted with dichloromethane and washed with sat NaHCO3. The organic phase was dried over MgSO4, filtered and concentrated. The crude product was added to a silica gel column and was eluted with ethyl acetate in hexanes (10-40%) to give the title compound (120 mg) as a yellow solid. In addition, mixed fractions were concentrated, applied to a silica gel column and eluted with methanol in dichloromethane (2-5%) to give an additional 19 mg of title compound for a combined yield of 139 mg (0.33 mmol, 53%). HRMS: [M+H]+ mass error=0.6 mDa or 1.45 ppm.

Fuente