Triphenylphosphine → N-Hydroxy-N-[1-[4-[4-(4-fluorophenyl)-5-(4-pyridyl)1H-imidazol-2-yl]phenyl]ethyl]urea

HRID 479769Notes

Reaction equation

HRID 479769 reaction equation
[CH3:1][CH:2](O)[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:10][C:11]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[N:13]=2)=[CH:5][CH:4]=1.P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([O:54][C:55]([NH:57][O:58]C(OCC1C=CC=CC=1)=O)=O)C1C=CC=CC=1.CCOC(/[N:74]=N/C(OCC)=O)=O>C1COCC1>[OH:58][N:57]([CH:2]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:10][C:11]([C:21]3[CH:22]=[CH:23][N:24]=[CH:25][CH:26]=3)=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=3)[N:13]=2)=[CH:5][CH:4]=1)[CH3:1])[C:55]([NH2:74])=[O:54]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 11822737N,O-bis(benzyloxycarbonyl)hydroxylamineHCID 54533644a-Methyl-4-[4-(4-fluorophenyl)-5-(4-pyridyl)imidazol-2-yl]benzyl alcohol

Product 1

HCID 18771543N-Hydroxy-N-[1-[4-[4-(4-fluorophenyl)-5-(4-pyridyl)1H-imidazol-2-yl]phenyl]ethyl]urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of a-Methyl-4-[4-(4-fluorophenyl)-5-(4-pyridyl)-imidazol-2-yl]benzyl alcohol (0.25 g, 0.70 mmol), P(Ph)3 (0.46 g, 1.75 mmol) and N,O-bis(benzyloxycarbonyl)hydroxylamine (0.48 g, 1.75 mmol) in THF (15 mL) was added DEAD (0.28 mL, 1.75 mmol) at rt. The reaction mixture was stirred at this temperature for 3 h and the solvent evaporated. The residue was partially purified by flash chromatography eluting with 1% MeOH/CHCl3. Methanol (25 mL) was added to this material and the mixture was cooled to −78° C. Ammonia was bubbled in at this temperature for 15 min. The reaction mixture was warmed slowly to rt, stoppered and stirred at rt for 2 days. The solvent was evaporated and the residue was purified by flash chromatography eluting with a solvent gradient of 1-10% MeOH/CHCl3. The title compound was obtained as an off-white solid (0.43 g, 14%): FABMS (m/z): 418 (M++H).

Workup

  1. customthe solvent evaporated
  2. customThe residue was partially purified by flash chromatography
  3. washeluting with 1% MeOH/CHCl3
  4. additionMethanol (25 mL) was added to this material
  5. customAmmonia was bubbled in at this temperature for 15 min
  6. temperatureThe reaction mixture was warmed slowly to rt
  7. stirringstirred at rt for 2 days
  8. customThe solvent was evaporated
  9. customthe residue was purified by flash chromatography
  10. washeluting with a solvent gradient of 1-10% MeOH/CHCl3

Sources & evidence

ORD record
ord-9acd093b492748ff9f67dbd43e3cc893
Source dataset
uspto-grants-2003_11
Patent number
US06645989B2

Reaction notes

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