Water → N-Phenyl-N'-(4-(6-(3,4,5-trimethoxyphenylamino)pyrimidin-4-yloxy)phenyl)urea hydrochloride

HRID 1010391Notes

Reaction equation

HRID 1010391 reaction equation
[Cl:1][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.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:31]=[C:32]([O:36][CH3:37])[C:33]=1[O:34][CH3:35])[NH2:30].C(OCC)(=O)C.O>CN1CCCC1=O.CCCCCC>[ClH:1].[C:19]1([NH:18][C:16]([NH:15][C:12]2[CH:13]=[CH:14][C:9]([O:8][C:4]3[CH:3]=[C:2]([NH:30][C:29]4[CH:31]=[C:32]([O:36][CH3:37])[C:33]([O:34][CH3:35])=[C:27]([O:26][CH3:25])[CH:28]=4)[N:7]=[CH:6][N:5]=3)=[CH:10][CH:11]=2)=[O:17])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl Acetate2×HCID 322853,4,5-TrimethoxyanilineHCID 22937019N-(4-(6-Chloropyrimidin-4-yloxy)phenyl)-N'-phenylurea

Product 1

HCID 22936469N-Phenyl-N'-(4-(6-(3,4,5-trimethoxyphenylamino)pyrimidin-4-yloxy)phenyl)urea hydrochlorideYield 48%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

N-(4-(6-Chloropyrimidin-4-yloxy)phenyl)-N′-phenylurea (68.0 mg, 0.200 mmol) and 3,4,5-trimethoxyaniline (183 mg, 1.00 mmol) were heated and stirred in 1-methylpyrrolidone (1 ml) at 150° C. for 2 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=3:1), the fraction containing the target substance was concentrated, converted to a hydrochloride with 1N hydrochloric acid and suspended in methanol, the suspension was diluted with ethyl acetate and the crystals were filtered out, washed with ethyl acetate and blow-dried to obtain the title compound (50.0 mg, 0.095 mmol, 48%) as light green 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 ethyl acetate
  9. filtrationthe crystals were filtered out
  10. washwashed with ethyl acetate
  11. customblow-dried

Sources & evidence

ORD record
ord-a575dd05596940239b71d2221f1be39e
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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