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

HRID 968898Notes

Reaction equation

HRID 968898 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](O)[N:9]=2)=[CH:4][CH:3]=1.C(#N)C.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[CH3:36][NH:37][S:38]([CH3:41])(=[O:40])=[O:39]>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:37]([CH3:36])[S:38]([CH3:41])(=[O:40])=[O:39])[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 73974-Toluenesulfonyl chlorideHCID 97632N-MethylmethanesulfonamideHCID 178496923Methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate

Product 1

HCID 9929821Methyl 4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinecarboxylateYield 69.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

In a 1000 mL-volume glass flask equipped with a stirrer, a thermometer and a reflux condenser were placed 50.0 g (172 mmol.) of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine, 20.8 g (189 mmol.) of sodium t-pentoxide, and 344 mL of acetonitrile, and the resulting mixture was stirred at 0-10° C. for 30 minutes. To the mixture was slowly added 36.1 g (189 mmol.) of p-toluenesulfonyl chloride, and the reaction was carried out at for 5 hours at room temperature. Subsequently, the reaction mixture was cooled to a temperature of 0-10° C. To the cooled reaction mixture were added 28.2 g (258 mmol.) of N-methylmethanesulfonamide and 26.5 g (241 mmol.) of sodium t-pentoxide. The mixture was kept at 0-10° C. for one hour and then heated to 75-82° C. for 2 hours under refluxing, to carry out a reaction. After the reaction was complete, the mixture was cooled to room temperature. To the cooled mixture was added 344 mL of water. The aqueous mixture was cooled to 0-10° C. and stirred for one hour, precipitating a crystalline product. The crystalline product was collected by filtration and dried, to obtain 45.3 g of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesulfonylamino)pyrimidine as a pale yellow crystalline product. The yield was 68% (based on the amount of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine).

Workup

  1. customIn a 1000 mL-volume glass flask equipped with a stirrer
  2. customwas carried out at for 5 hours at room temperature
  3. temperatureSubsequently, the reaction mixture was cooled to a temperature of 0-10° C
  4. customTo the cooled reaction mixture
  5. waitThe mixture was kept at 0-10° C. for one hour
  6. temperatureheated to 75-82° C. for 2 hours
  7. temperatureunder refluxing
  8. customa reaction
  9. temperaturethe mixture was cooled to room temperature
  10. temperatureThe aqueous mixture was cooled to 0-10° C.
  11. stirringstirred for one hour
  12. customprecipitating a crystalline product
  13. filtrationThe crystalline product was collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-65fbfac2260c4d08ae9be1607ac7df4d
Source dataset
uspto-grants-2007_12
Patent number
US07304156B2

Reaction notes

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