Reaction #1531309

Reaction equation

4-(4-fluoro-phenyl)-6-(2-(R)-methyl-piperazin-1-yl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine

2,5-dibromo-3-methyl-pyridine

DIEA

→

title compound

4-[4-(5-bromo-3-methyl-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine

Solvents

DMA

water

Conditions

Workup

1. 1
   TemperatureHeat
2. 2
   Extractionextract with EtOAc
3. 3
   Washwash with brine
4. 4
   DryingDry the organic layer (Na2SO4)
5. 5
   Concentrationconcentrate under reduced pressure
6. 6
   OtherPurify the residue by flash column chromatography
7. 7
   Washeluting with EtOAc-Hexanes (1:10)

Procedure

Heat a mixture of 4-(4-fluoro-phenyl)-6-(2-(R)-methyl-piperazin-1-yl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine (400 mg, 1.13 mmol), 2,5-dibromo-3-methyl-pyridine (367 mg, 1.46 mmol), and DIEA (218 mg, 1.69 mmol) in DMA at 135° C. for 96 h. Dilute with water, extract with EtOAc, and wash with brine. Dry the organic layer (Na2SO4) and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with EtOAc-Hexanes (1:10) to afford the title compound as a white solid.

Source