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

HRID 1160657Notes

Reaction equation

HRID 1160657 reaction equation
[CH3:1][NH:2][S:3]([CH3:6])(=[O:5])=[O:4].C(#N)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]([CH:27]([CH3:29])[CH3:28])[N:20]=[C:19](OS(C3C=CC(C)=CC=3)(=O)=O)[N:18]=2)=[CH:13][CH:12]=1>O>[F:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]([CH:27]([CH3:29])[CH3:28])[N:20]=[C:19]([N:2]([CH3:1])[S:3]([CH3:6])(=[O:5])=[O:4])[N:18]=2)=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 97632N-MethylmethanesulfonamideHCID 17989602Rosuvastatin Impurity 162

Product 1

HCID 9929821Methyl 4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinecarboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
81.5 °C

Procedure

In a 25 mL-volume glass flask equipped with a stirrer, a thermometer and a reflux condenser were placed 196 mg (1.8 mmol.) of N-methylmethanesulfonamide, 198 mg (1.8 mmol.) of sodium t-pentoxide, 7.5 mL of acetonitrile, and 667 mg (1.5 mmol.) of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(p-toluenesulfonyloxy)pyrimidine. The mixture was heated to 81-82° C. for 1.5 hours under refluxing, to carry out reaction. After the reaction was complete, the reaction mixture was cooled to room temperature. To the cooled mixture was added 10 mL of water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate portion was separated, and dried over anhydrous magnesium sulfate. The dried ethyl acetate portion was filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (column: Wako Gel C-200, eluent: hexane/ethyl acetate (2:1, volume ratio)). There was obtained 428 mg of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesulfonylamino)-pyrimidine. The yield was 75% (based on the amount of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(p-toluenesulfonyloxy)pyrimidine).

Workup

  1. customIn a 25 mL-volume glass flask equipped with a stirrer
  2. temperatureunder refluxing
  3. customreaction
  4. temperaturethe reaction mixture was cooled to room temperature
  5. extractionthe aqueous mixture was extracted with ethyl acetate
  6. customThe ethyl acetate portion was separated
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe dried ethyl acetate portion was filtered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (column: Wako Gel C-200, eluent: hexane/ethyl acetate (2:1, volume ratio))

Sources & evidence

ORD record
ord-e1f8cb9b939c4a99a87e7268de4e0409
Source dataset
uspto-grants-2010_10
Patent number
US07816528B2

Reaction notes

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