Water → N-(4-(6-(2-Fluorophenylamino)pyrimidin-4-yloxy)phenyl)-N'-phenylurea

HRID 1433660Notes

Reaction equation

HRID 1433660 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:17])=[CH:11][CH:10]=2)[CH:3]=1.[F:25][C:26]1[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=1[NH2:28].C(OCC)(=O)C.O>CN1CCCC1=O.CCCCCC>[F:25][C:26]1[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=1[NH:28][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:17])=[CH:11][CH:10]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl Acetate2×HCID 95842-FluoroanilineHCID 22937019N-(4-(6-Chloropyrimidin-4-yloxy)phenyl)-N'-phenylurea

Product 1

HCID 22936905N-(4-(6-(2-Fluorophenylamino)pyrimidin-4-yloxy)phenyl)-N'-phenylureaYield 31%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

N-(4-(6-Chloropyrimidin-4-yloxy)phenyl)-N′-phenyl urea (68.0 mg, 0.200 mmol) and 2-fluoroaniline (111 mg, 1.00 mmol) were heated and stirred in 1-methylpyrrolidone (1 ml) at 170° C. for 3 hours. The reaction solution was distributed between ethyl acetate and water, the organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated brine and dried over anhydrous magnesium sulfate, the drying agent was filtered off and the filtrate was distilled off under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (eluent—ethyl acetate:hexane=3:2), the fraction containing the target substance was concentrated and suspended in ethyl acetate, the suspension was diluted with hexane and the crystals were filtered out, washed with hexane and blow-dried to obtain the title compound (26.0 mg, 0.062 mmol, 31%) as colorless crystals.

Workup

  1. washthe organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationthe drying agent was filtered off
  4. distillationthe filtrate was distilled off under reduced pressure
  5. customThe obtained crude product
  6. additionthe fraction containing the target substance
  7. concentrationwas concentrated
  8. additionthe suspension was diluted with hexane
  9. filtrationthe crystals were filtered out
  10. washwashed with hexane
  11. customblow-dried

Sources & evidence

ORD record
ord-135a245d57eb463098947a543caedc46
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

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