反応 #84140

反応方程式

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

収率 55.0%

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

収率 55.0%

溶媒

EtOAc

H2O

1,4-dioxane H2O

反応条件

後処理

1. 1
   その他the layers separated
2. 2
   洗浄The organic phase was washed with saturated brine solution (50 mL)
3. 3
   乾燥dried (MgSO4)
4. 4
   ろ過filtered
5. 5
   その他the solvent evaporated in vacuo
6. 6
   その他The crude product was purified by column chromatography (40-63 mesh silica gel, 1:1 isohexane-EtOAc)

実験手順

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+).

出典