تفاعل #84140

معادلة التفاعل

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

المردود 55.0%

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

المردود 55.0%

المذيبات

EtOAc

H2O

1,4-dioxane H2O

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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+).

المصدر