반응 #84140

반응 방정식

2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinonitrile

5-boranyl-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

2,4-dichloropyrimidine

Na2CO3

→

title compound

수율 55.0%

5-(2-Chloro-primidin-4-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

수율 55.0%

용매

EtOAc

H2O

1,4-dioxane H2O

반응 조건

후처리

1. 1
   기타the layers separated
2. 2
   세척The organic phase was washed with saturated brine solution (50 mL)
3. 3
   건조dried (MgSO4)
4. 4
   여과filtered
5. 5
   기타the solvent evaporated in vacuo
6. 6
   기타The crude product was purified by column chromatography (40-63 mesh silica gel, 1:1 isohexane-EtOAc)

실험 절차

A mixture of 2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinonitrile and 5-boranyl-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile (7) (2.64 g, ˜9.6 mmol), 2,4-dichloropyrimidine (1.2 g, 9.6 mmol), tetrakis(triphenylphosphine)palladium(0) (1.1 g, 1.0 mmol) and Na2CO3 (3.1 g, 28.8 mmol) were dissolved in 1:1 1,4-dioxane-H2O (40 mL) and the mixture was stirred at 120° C. in the microwave (250 W, stirring) for 30 minutes. The mixture was diluted with EtOAc (130 mL) and H2O (40 mL) and the layers separated. The organic phase was washed with saturated brine solution (50 mL), then dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by column chromatography (40-63 mesh silica gel, 1:1 isohexane-EtOAc) to provide the title compound as a pale yellow solid (1.6 g, 55%); LCMS, Rt=2.80 min (MeOH-FA method), m/z 304 (MH+).

출처