3,5-Bis(trifluoromethyl)phenyl isocyanate → 3-(3,5-Bis(trifluoromethyl)phenyl)-1-(4-tert-butylcyclohexyl)-1-{4-[1-hydroxy-2-(2H-tetrazol-5-yl)ethyl]benzyl}urea

HRID 480377Notes

Reaction equation

HRID 480377 reaction equation
[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]([OH:26])[CH2:20][C:21]3[N:22]=[N:23][NH:24][N:25]=3)=[CH:15][CH:14]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[F:27][C:28]([F:43])([F:42])[C:29]1[CH:30]=[C:31]([N:39]=[C:40]=[O:41])[CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1>C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C>[F:27][C:28]([F:42])([F:43])[C:29]1[CH:30]=[C:31]([NH:39][C:40](=[O:41])[N:11]([CH:8]2[CH2:7][CH2:6][CH:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:10][CH2:9]2)[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]([OH:26])[CH2:20][C:21]3[N:22]=[N:23][NH:24][N:25]=3)=[CH:15][CH:14]=2)[CH:32]=[C:33]([C:35]([F:38])([F:36])[F:37])[CH:34]=1

Participants

4

Reactant 2

HCID 27333143,5-Bis(trifluoromethyl)phenyl isocyanateHCID 187688861-{4-[(4-tert-butylcyclohexylamino)methyl]phenyl}-2-(2H-tetrazol-5-yl)ethanol

Product 1

HCID 187689003-(3,5-Bis(trifluoromethyl)phenyl)-1-(4-tert-butylcyclohexyl)-1-{4-[1-hydroxy-2-(2H-tetrazol-5-yl)ethyl]benzyl}urea

Reagents, catalysts & solvents 1

HCID 6913588N,O-bis(trimethylsilyl)acetamideSolvent

Procedure

Resin bound 1-{4-[(4-tert-butylcyclohexylamino)methyl]phenyl}-2-(2H-tetrazol-5-yl)ethanol (50 mg) was suspended in DCP (500 μl) and N,O-bis(trimethylsilyl)acetamide (100 μl) was added. The mixture was shaken at room temperature for 1 hour, then a solution of 3,5-bis(trifluoromethyl)phenylisocyanate (48 mg, 0.19 mmol) in DCP (500 μl) was added. The resin mixture was shaken overnight at room temperature, then drained and washed with DCM (3×2 ml); DMF (3×2 ml); water (2×2 ml, each 20 min washes), THF (3×2 ml) and finally DCM (6×2 ml). The resin was then treated with 50% TFA in DCM for 30 min. Solvent was collected by filtration, and taken to dryness by evaporation in vacuo.

Workup

  1. additionwas added
  2. stirringThe resin mixture was shaken overnight at room temperature
  3. washwashed with DCM (3×2 ml)
  4. customeach 20 min washes
  5. additionThe resin was then treated with 50% TFA in DCM for 30 min
  6. filtrationSolvent was collected by filtration
  7. customtaken to dryness by evaporation in vacuo

Sources & evidence

ORD record
ord-dbc9ae6f8cc24dc0bad7d8cc99cc43f2
Source dataset
uspto-grants-2003_11
Patent number
US06649641B2

Reaction notes

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