Reacción #157828

Ecuación de reacción

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

Disolventes

ethyl acetate

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITThe reaction solution was left
2. 2
   Temperaturato cool
3. 3
   Filtraciónfollowed by filtration through celite
4. 4
   ExtracciónThe filtrate was extracted with ethyl acetate
5. 5
   LavadoThe organic layer was washed with water and brine
6. 6
   Secadodried over anhydrous magnesium sulfate
7. 7
   Otroafter which the solvent was evaporated under reduced pressure
8. 8
   OtroThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:4)

Procedimiento

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%).

Fuente