1,1'-Carbonyldiimidazole → 1H-imidazole-1-carboxylic acid

HRID 1826843Notes

Reaction equation

HRID 1826843 reaction equation
[O:1]([C:8]1[CH:15]=[CH:14][CH:13]=[C:12]([NH:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])[C:9]=1CN)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25](N1C=CN=C1)([N:27]1[CH:31]=[CH:30][N:29]=[CH:28]1)=[O:26]>O1CCCC1>[N:27]1([C:25]([OH:26])=[O:1])[CH:31]=[CH:30][N:29]=[CH:28]1.[F:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:17]=1[NH:16][C:12]1[CH:13]=[CH:14][CH:15]=[C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:9]=1[NH-:27]

Participants

5

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 22136222HCID 22136222, compound

Product 2

HCID 30171271H-imidazole-1-carboxylic acidHCID 178514219HCID 178514219, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The product of example 1c above, 2-phenoxy-6-(2,6-difluorophenylamino)benzylamine, (0.159 g 0.49 mmol) was dissolved in dry tetrahydrofuran (6 mL) and stirred under argon at room temperature. 1,1′-Carbonyldiimidazole (0.102 g, 0.63 mmol) dissolved in dry tetrahydrofuran (4 mL) was added and the mixture stirred at room temperature, and then heated to reflux The solvent was evaporated in vacuo, to give a crude product which was flash chromatographed on silica gel eluted with 0–3% methanol in methylene chloride to give an intermediate imidazole-1-carboxylic acid[2-(2,6-difluorophenylamino)-6-phenoxyphenylamide. The imidazole-1-carboxylic acid[2-(2,6-difluorophenylamino)-6-phenoxyphenylamide was dissolved in tetrahydrofuran (5 mL) and sodium hydride hydride, dry, 95% (0.025 g, 1 mmol) was added. The resulting mixture was stirred for four hours under argon. The solvent was evaporated and the residue was partioned between ethyl acetate and water. The organic phase was washed with brine, dried over anhydrous Na2SO4, filtered, and evaporated to give the crude product which was then chromatographed on silica gel eluted with 0–20% ethyl acetate in CH2Cl2 to give the title compound as a white amorphous solid. mp 199–201° C.

Workup

  1. additionwas added
  2. stirringthe mixture stirred at room temperature
  3. temperatureheated
  4. temperatureto reflux The solvent
  5. customwas evaporated in vacuo
  6. customto give a crude product which
  7. customchromatographed on silica gel
  8. washeluted with 0–3% methanol in methylene chloride

Sources & evidence

ORD record
ord-fb0a6e508260495bb5451b3a25dff715
Source dataset
uspto-grants-2006_05
Patent number
US07053099B1

Reaction notes

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