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

HRID 1915022Notes

Reaction equation

HRID 1915022 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(C3C=CC(C)=CC=3)(=O)=O)[N:9]=2)=[CH:4][CH:3]=1.[CH3:32][NH:33][S:34]([CH3:37])(=[O:36])=[O:35].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC(C)=O.O>[F:1][C:2]1[CH:3]=[CH:4][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:33]([CH3:32])[S:34]([CH3:37])(=[O:36])=[O:35])[N:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 97632N-MethylmethanesulfonamideHCID 17989602Rosuvastatin Impurity 1622×

Product 1

HCID 9929821Methyl 4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinecarboxylateYield 63%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 180AcetoneSolventHCID 962WaterSolvent2×

Conditions

Temperature
85 °C

Procedure

In a 50 mL-volume glass flask equipped with a stirrer, a thermometer and a reflux condenser were placed 1.1 g (2.5 mmol.) of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(p-toluenesulfonyloxy)-pyrimidine, 0.55 g (5.0 mmol.) of N-methylmethanesulfonamide, 0.69 g (5.0 mmol.) of potassium carbonate (available from Wako Junyaku Co., Ltd., special grade), 0.32 g (1.0 mmol.) of tetrabutylammonium bromide, 20 mL of toluene and 5 mL of water. The mixture was heated to 85° C. for 28 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 analyzed by high performance liquid chromatography. It was confirmed that 0.6 g of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesulfonylamino)pyrimidine was produced. The yield was 63% (based on the amount of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(p-toluenesulfonyloxy)-pyrimidine).

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. customwas produced

Sources & evidence

ORD record
ord-3d2e7948197848b4a17a4c369b592375
Source dataset
uspto-grants-2013_12
Patent number
US08614320B2

Reaction notes

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