Potassium Carbonate → Methyl 4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinecarboxylate

HRID 1515143Notes

Reaction equation

HRID 1515143 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH:18]([CH3:20])[CH3:19])[N:11]=[C:10](OS(C(F)(F)F)(=O)=O)[N:9]=2)=[CH:4][CH:3]=1.[CH3:29][NH:30][S:31]([CH3:34])(=[O:33])=[O:32].C(=O)([O-])[O-].[K+].[K+].C(OCCCC)(=O)C>CC(C)=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH:18]([CH3:20])[CH3:19])[N:11]=[C:10]([N:30]([CH3:29])[S:31]([CH3:34])(=[O:33])=[O:32])[N:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31272Butyl AcetateHCID 97632N-MethylmethanesulfonamideHCID 179896104-Fluorophenyl-6-isopropyl-5-methoxycarbonyl-2-trifluoromethanesulfonyloxypyrimidine

Product 1

HCID 9929821Methyl 4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinecarboxylateYield 78.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
123.5 °C

Procedure

In a 50 mL-volume glass flask equipped with a stirrer, a thermometer and a reflux condenser were placed 3.0 g (7 mmol.) of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-trifluoromethanesulfonyloxypyrimidine, 1.13 g (10.5 mmol.) of N-methylmethanesulfonamide, 1.45 g (10.5 mmol.) of potassium carbonate (available from Wako Junyaku Co., Ltd., special grade), and 14 mL of butyl acetate. The mixture was heated to 122-125° C. for 3 hours under refluxing, to carry out reaction. After the reaction was complete, the reaction mixture was cooled to room temperature. To the reaction mixture were added 10 mL of water and 7 mL of acetone, and the organic liquid portion was separated. The organic liquid portion was washed with a saturated aqueous sodium chloride solution and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (column: Wako Gel C-200, eluent: hexane/ethyl acetate (5:1, volume ratio)). There was obtained 2.1 g of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesul-fonylamino)pyrimidine as a white crystalline product. The yield was 78% (based on the amount of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-trifluoromethanesulfonyloxypyrimidine).

Workup

  1. customIn a 50 mL-volume glass flask equipped with a stirrer
  2. temperatureunder refluxing
  3. customreaction
  4. temperaturethe reaction mixture was cooled to room temperature
  5. customthe organic liquid portion was separated
  6. washThe organic liquid portion was washed with a saturated aqueous sodium chloride solution
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (column: Wako Gel C-200, eluent: hexane/ethyl acetate (5:1, volume ratio))

Sources & evidence

ORD record
ord-88d5898276c1468dac0209b5c97bc094
Source dataset
uspto-grants-2012_07
Patent number
US08222412B2

Reaction notes

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