Reaktion #164586

Reaktionsgleichung

7-bromo-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one

Intermediate 24A

7-bromo-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one

1,4-diazabicyclo[3.2.2]nonane

sodium t-butoxide

(+/−) BINAP

→

7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one

Ausbeute 35.0%

Lösungsmittel

water

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeReaction mixture
2. 2
   Temperaturto cool to room temperature
3. 3
   Extraktionthe product extracted into ethyl acetate
4. 4
   TrocknenOrganics washed several times with water, dried (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   Sonstigeevaporated to dryness
7. 7
   workup.ADDITIONThe crude product was added to a silica gel column (25 g)
8. 8
   Waschenwas eluted with 0-50% 2M ammonia in methanol in ethylacetate

Vorschrift

A mixture of 7-bromo-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one (Intermediate 24A) (50 mg, 0.143 mmol), 1,4-diazabicyclo[3.2.2]nonane (27.2 mg, 0.215 mmol), sodium t-butoxide (55.1 mg, 0.574 mmol), tris(dibenzylideneacetone)dipalladium(0) (13.13 mg, 0.014 mmol) and (+/−) BINAP (26.8 mg, 0.043 mmol) in degassed dioxane (1 mL) was heated to 85° C. under N2 in a sealed vessel overnight. Reaction mixture allowed to cool to room temperature, diluted with water and the product extracted into ethyl acetate. Organics washed several times with water, dried (MgSO4), filtered and then evaporated to dryness. The crude product was added to a silica gel column (25 g) and was eluted with 0-50% 2M ammonia in methanol in ethylacetate to afford 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one (19.4 mg, 0.05 mmol).

Quelle