Reaction #84140

Reaction equation

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

Yield 55.0%

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

Yield 55.0%

Solvents

EtOAc

H2O

1,4-dioxane H2O

Conditions

Workup

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

Procedure

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