Sodium Carbonate → 5-(2-Chloro-pyrimidin-4-yl)-2-pyrrolidin-1-yl-benzonitrile

Temperature

100 °C

Pyrrolidin-1-yl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (200 mg, 0.67 mmol), 2,4-dichloropyrimidine (120 mg, 0.81 mmol), tetrakis(triphenylphosphine)palladium(0) (78 mg, 0.07 mmol, 10 mol %) and sodium carbonate (213 mg, 2.01 mmol) were diluted with 1:1 1,4-dioxane-H2O (4.0 mL). The mixture was then heated at 100° C. in the microwave (300 W, stirring) for 10 minutes. The reaction was repeated four more times. The reaction mixtures were combined and the solvents evaporated in vacuo (Genevac™). The residue was partitioned between DCM (150 mL) and H2O (50 mL). The organic phase was washed with water (50 mL) and saturated brine solution (75 mL). The organic phase was then dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by column chromatography (40-63 mesh silica gel, 70% isohexane-EtOAc) to provide the title compound as a yellow solid (727 mg, 76%); LC-MS, Rt=2.80 min (MeOH-FA method), m/z 285, 287 (MH+).

1. customThe reaction mixtures
2. customthe solvents evaporated in vacuo (Genevac™)
3. customThe residue was partitioned between DCM (150 mL) and H2O (50 mL)
4. washThe organic phase was washed with water (50 mL) and saturated brine solution (75 mL)
5. dry with materialThe organic phase was then dried (MgSO4)
6. filtrationfiltered
7. customthe solvent evaporated in vacuo
8. customThe crude product was purified by column chromatography (40-63 mesh silica gel, 70% isohexane-EtOAc)

ORD record

ord-25f1dc9559af4adca23c16b6708af903

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962609B2