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

HRID 2195043Notes

Reaction equation

HRID 2195043 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([N:15]2[CH2:19][CH2:18][CH2:17][CH:16]2[CH3:20])[N:3]=1.[Br:21][C:22]1[CH:23]=[C:24]([CH3:35])[C:25]([N:28]2[CH2:33][CH2:32][NH:31][C@H:30]([CH3:34])[CH2:29]2)=[N:26][CH:27]=1.C([O-])(O)=O.[Na+]>CCO>[Br:21][C:22]1[CH:23]=[C:24]([CH3:35])[C:25]([N:28]2[CH2:33][CH2:32][N:31]([C:2]3[CH:7]=[C:6]([C:8]4[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=4)[N:5]=[C:4]([N:15]4[CH2:19][CH2:18][CH2:17][CH:16]4[CH3:20])[N:3]=3)[C@H:30]([CH3:34])[CH2:29]2)=[N:26][CH:27]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 121612594-Chloro-6-(4-fluorophenyl)-2-(2-methylpyrrolidin-1-yl)pyrimidineHCID 574734721-(5-Bromo-3-methyl-pyridin-2-yl)-3-(R)-methyl-piperazine

Product 1

HCID 591682484-[4-(5-Bromo-3-methyl-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Heat a mixture of 4-chloro-6-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidine (1.30 g, 4.44 mmol), 1-(5-bromo-3-methyl-pyridin-2-yl)-3-(R)-methyl-piperazine (1.2 g, 4.44 mmol), and NaHCO3 (0.71 g, 8.46 mmol) in EtOH at 50° C. for 20 h. Concentrate under reduced pressure and partition between EtOAc and brine. Dry the organic layer (Na2SO4) and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with EtOAc-hexanes (1:4) to afford the title compound as a white solid.

Workup

  1. temperatureHeat
  2. concentrationConcentrate under reduced pressure
  3. custompartition between EtOAc and brine
  4. dry with materialDry the organic layer (Na2SO4)
  5. concentrationconcentrate under reduced pressure
  6. customPurify the residue by flash column chromatography
  7. washeluting with EtOAc-hexanes (1:4)

Sources & evidence

ORD record
ord-fc73f281abcf4394a8ef26b6c18fd3df
Source dataset
uspto-grants-2012_12
Patent number
US08334382B2

Reaction notes

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