Sulfuric Acid → HCID 178500118, compound

HRID 2065800Notes

Reaction equation

HRID 2065800 reaction equation
CS(O)(=O)=O.N[C:7]1[N:12]=[C:11]([C:13]2[N:14]=[C:15]([C:26]([CH3:32])([CH3:31])[C:27]([O:29][CH3:30])=[O:28])[NH:16][C:17]=2[C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])[CH:10]=[CH:9][C:8]=1[N+:33]([O-:35])=[O:34].S(=O)(=O)(O)[OH:37].N([O-])=O.[Na+].P([O-])(O)(O)=O.[Na+]>O.C1COCC1.CS(C)=O>[F:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[C:17]1[NH:16][C:15]([C:26]([CH3:31])([CH3:32])[C:27]([O:29][CH3:30])=[O:28])=[N:14][C:13]=1[C:11]1[CH:10]=[CH:9][C:8]([N+:33]([O-:35])=[O:34])=[C:7]([OH:37])[N:12]=1

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 23668193Sodium NitriteHCID 23672064Monosodium phosphateHCID 178500117HCID 178500117, compound

Product 1

HCID 178500118HCID 178500118, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22.5 °C

Procedure

Under a nitrogen atmosphere methyl 2-[4-(6-amino-5-nitro-2-pyridyl)-5-(2,4-difluorophenyl)-1H-imidazol-2-yl]-2-methyl-propanoate methanesulfonate (68.9 g, 134.2 mmol), dimethyl sulfoxide (275.5 mL), THF (116.2 mL), and water (303.2 mL) are added and the mixture is stirred at 20-25° C. Sulfuric acid 95-97% (93.6 mL) is added dropwise to the reaction mixture and the temperature is maintained below 30° C. The reaction mixture is cooled to 0-5° C., and a solution of sodium nitrite (18.6 g, 0.27 mmol) in water (82.7 mL) is added at 0-10° C. The reaction mixture is stirred for 1-2 h at this temperature. 10% Aqueous sodium dihydrogen phosphate (930.0 mL) is added dropwise to maintain the temperature below 25° C. The resulting mixture is stirred for 2-3 h at 15-25° C., and the solids are collected by filtration. The filtercake is washed with water (138 mL) and the solids are transferred into a reaction vessel. Methanol (566 mL) is added and the mixture is heated to 60-65° C. for 1-2 h. Water (87 mL) is added and the mixture is stirred at 60-65° C. for 1-2 h. The reaction mixture is cooled to 15-25° C. and the mixture is stirred at 15-25° C. for 2-4 h. The mixture is filtered, the cake is washed with methanol (87 mL), and is dried under a vacuum below 70° C. to provide the title compound as a yellow solid (53.28 g, 93%).

Workup

  1. temperaturethe temperature is maintained below 30° C
  2. temperatureThe reaction mixture is cooled to 0-5° C.
  3. stirringThe reaction mixture is stirred for 1-2 h at this temperature
  4. temperatureto maintain the temperature below 25° C
  5. stirringThe resulting mixture is stirred for 2-3 h at 15-25° C.
  6. filtrationthe solids are collected by filtration
  7. washThe filtercake is washed with water (138 mL)
  8. customthe solids are transferred into a reaction vessel
  9. additionMethanol (566 mL) is added
  10. temperaturethe mixture is heated to 60-65° C. for 1-2 h
  11. additionWater (87 mL) is added
  12. stirringthe mixture is stirred at 60-65° C. for 1-2 h
  13. temperatureThe reaction mixture is cooled to 15-25° C.
  14. stirringthe mixture is stirred at 15-25° C. for 2-4 h
  15. filtrationThe mixture is filtered
  16. washthe cake is washed with methanol (87 mL)
  17. customis dried under a vacuum below 70° C.

Sources & evidence

ORD record
ord-34ab10c97cfd47ed8d9ed80e9662625d
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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