Potassium Carbonate → 4-[4-(5-Bromo-3-methyl-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-2-chloro-6-(4-fluoro-phenyl)-pyrimidine

HRID 2195088Notes

Reaction equation

HRID 2195088 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[N:3]=1.[Br:16][C:17]1[CH:18]=[C:19]([CH3:30])[C:20]([N:23]2[CH2:28][CH2:27][NH:26][C@H:25]([CH3:29])[CH2:24]2)=[N:21][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CC(N(C)C)=O>[Br:16][C:17]1[CH:18]=[C:19]([CH3:30])[C:20]([N:23]2[CH2:28][CH2:27][N:26]([C:6]3[CH:5]=[C:4]([C:9]4[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=4)[N:3]=[C:2]([Cl:1])[N:7]=3)[C@H:25]([CH3:29])[CH2:24]2)=[N:21][CH:22]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 116373222,4-Dichloro-6-(4-fluorophenyl)pyrimidineHCID 574734721-(5-Bromo-3-methyl-pyridin-2-yl)-3-(R)-methyl-piperazine

Product 1

HCID 591683034-[4-(5-Bromo-3-methyl-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-2-chloro-6-(4-fluoro-phenyl)-pyrimidine

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Heat a mixture of 2,4-dichloro-6-(4-fluoro-phenyl)-pyrimidine (6.0 g, 24.7 mmol), 1-(5-bromo-3-methyl-pyridin-2-yl)-3-(R)-methyl-piperazine (7.0 g, 25.9 mmol) and K2CO3 (6.8 g, 49.4 mmol) in DMA at 60° C. for 16 h. Partition the mixture between EtOAc and water, dry (Na2SO4) the organic layer and concentrate under reduced pressure. Purify with flash silica gel column eluting with 15% EtOAc/hexanes. Concentrate under reduced pressure to give the title compound.

Workup

  1. temperatureHeat
  2. customPartition the mixture between EtOAc and water
  3. dry with materialdry (Na2SO4) the organic layer
  4. concentrationconcentrate under reduced pressure
  5. customPurify with flash silica gel column
  6. washeluting with 15% EtOAc/hexanes
  7. concentrationConcentrate under reduced pressure

Sources & evidence

ORD record
ord-0a3965c991ad4827913af75bf3f78286
Source dataset
uspto-grants-2012_12
Patent number
US08334382B2

Reaction notes

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