반응 #157828

반응 방정식

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

용매

ethyl acetate

N,N-dimethylformamide

반응 조건

후처리

1. 1
   workup.WAITThe reaction solution was left
2. 2
   온도to cool
3. 3
   여과followed by filtration through celite
4. 4
   추출The filtrate was extracted with ethyl acetate
5. 5
   세척The organic layer was washed with water and brine
6. 6
   건조dried over anhydrous magnesium sulfate
7. 7
   기타after which the solvent was evaporated under reduced pressure
8. 8
   기타The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:4)

실험 절차

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%).

출처