Réaction #84140

Équation de réaction

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

Rendement 55.0%

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

Rendement 55.0%

Solvants

EtOAc

H2O

1,4-dioxane H2O

Conditions de réaction

Traitement

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

Mode opératoire

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+).

Source