4-Fluorophenyl isocyanate → N-(4-{2-[(Cyclopropylmethyl)aminocarbonyl]pyridin-4-yl}oxyphenyl)-N'-(4-fluorophenyl)urea

HRID 1010318Notes

Reaction equation

HRID 1010318 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH:15][CH2:16][CH:17]3[CH2:19][CH2:18]3)=[O:14])[CH:8]=2)=[CH:4][CH:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=1>O1CCCC1>[CH:17]1([CH2:16][NH:15][C:13]([C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:20]=[CH:21][C:2]([NH:1][C:30]([NH:29][C:26]4[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=4)=[O:31])=[CH:3][CH:4]=3)[CH:12]=[CH:11][N:10]=2)=[O:14])[CH2:19][CH2:18]1

Participants

4

Reactant 2

HCID 709554-Fluorophenyl isocyanateHCID 589311534-(4-Aminophenoxy)-N-(cyclopropylmethyl)picolinamide

Product 1

HCID 58930960N-(4-{2-[(Cyclopropylmethyl)aminocarbonyl]pyridin-4-yl}oxyphenyl)-N'-(4-fluorophenyl)urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

After adding 100 mg of 4-(4-Aminophenoxy)-2-[(cyclopropylmethyl)aminocarbonyl]pyridine to 5 ml of tetrahydrofuran, 0.075 ml of p-fluorophenyl isocyanate was added at room temperature and the mixture was stirred for 1 hour. NH type silica gel was added to the reaction solution, the solvent was distilled off under reduced pressure and the reaction product was adsorbed onto the silica gel. The silica gel was charged into a dry column packed with NH type silica gel, and column purification was performed (hexane:ethyl acetate=1:1, followed by ethyl acetate and ethyl acetate:methanol=10:1). The solvent was distilled off under reduced pressure, ethyl acetate and hexane were added to the residue, and the precipitated solid was filtered out to obtain 25 mg of the target substance as a light yellow powder.

Workup

  1. additionwas added at room temperature
  2. additionNH type silica gel was added to the reaction solution
  3. distillationthe solvent was distilled off under reduced pressure
  4. additionThe silica gel was charged into a dry column
  5. custompacked with NH type silica gel, and column purification
  6. distillationThe solvent was distilled off under reduced pressure, ethyl acetate and hexane
  7. additionwere added to the residue
  8. filtrationthe precipitated solid was filtered out
  9. customto obtain 25 mg of the target substance as a light yellow powder

Sources & evidence

ORD record
ord-c06b3bfda0bb48d4b8cd525dbe78273f
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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