Urea → HCID 59547881, compound

HRID 1946339Notes

Reaction equation

HRID 1946339 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]([C:25]([F:28])([F:27])[F:26])=[C:6]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:24])[C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])=[N:10]2)[CH:7]=1.N([O-])=[O:30].[Na+].NC(N)=O>O.ClCCl.S([O-])([O-])(=O)=O.[Cu+2]>[F:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([F:22])[C:16]=1[C:15]([NH:14][C:11]1[CH:12]=[CH:13][N:9]([CH2:8][C:6]2[CH:7]=[C:2]([OH:30])[CH:3]=[CH:4][C:5]=2[C:25]([F:28])([F:27])[F:26])[N:10]=1)=[O:24]

Participants

7

Reactant 3

HCID 1176UreaHCID 23668193Sodium NitriteHCID 59547994HCID 59547994, compound

Product 1

HCID 59547881HCID 59547881, compound

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

To a suspension of N-(1-{[5-amino-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide (for a preparation see Intermediate 41) (1.0 g, 2.52 mmol) in water (15 ml) in an ice-water bath was added a solution of sodium nitrite (0.346 g, 5.01 mmol, Aldrich) in water (3 ml). The solution was maintained at 0-10° C. for 20 min. To the solution was added urea (0.94 g, 15.65 mmol, Aldrich) and then copper (II) sulphate (0.139 g, 0.868 mmol, Fluka). The mixture was heated to 90° C. for 30 min. The mixture was partitioned between water (150 ml) and ethyl acetate (130 ml). The phases were separated and the aqueous phase washed with ethyl acetate (50 ml). The combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave an oil. The residue was loaded in dichloromethane and purified on silica 100 g using a 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an orange solid (0.462 g); LCMS: (System 4) MH+=398, tRET=2.36 min.

Workup

  1. temperatureThe mixture was heated to 90° C. for 30 min
  2. customThe mixture was partitioned between water (150 ml) and ethyl acetate (130 ml)
  3. customThe phases were separated
  4. washthe aqueous phase washed with ethyl acetate (50 ml)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customto leave an oil
  9. custompurified on silica 100 g
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-1a9923470de74d1ea241790d6a8d7a03
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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