Reaktion #157828

Reaktionsgleichung

water

(5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(tributylstannyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

cesium fluoride

6-iodo-2-methoxypyridin-3-amine

→

(5R)-5-[(E)-2-(5-amino-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

Lösungsmittel

ethyl acetate

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITThe reaction solution was left
2. 2
   Temperaturto cool
3. 3
   Filtrationfollowed by filtration through celite
4. 4
   ExtraktionThe filtrate was extracted with ethyl acetate
5. 5
   WaschenThe organic layer was washed with water and brine
6. 6
   Trocknendried over anhydrous magnesium sulfate
7. 7
   Sonstigeafter which the solvent was evaporated under reduced pressure
8. 8
   SonstigeThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:4)

Vorschrift

Tetrakis(triphenylphosphine)palladium(0) (50 mg) was added to a solution of (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(tributylstannyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one obtained in Reference Example 4-26 (296 mg), 6-iodo-2-methoxypyridin-3-amine obtained in Reference Example 4-31(1) (220 mg), cesium fluoride (135 mg) and copper iodide (93 mg) in N,N-dimethylformamide (1.5 mL) in a nitrogen atmosphere, and the mixture was stirred at 65° C. for three hours. The reaction solution was left to cool, and then water and ethyl acetate were added, followed by filtration through celite. The filtrate was extracted with ethyl acetate. The organic layer was washed with water and brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:4) to give (5R)-5-[(E)-2-(5-amino-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one as a light brown amorphous (152 mg, 68%).

Quelle