1-Bromo-2-Chloroethane → N-(4-(6-Cyano-7-(2-chloroethoxy)-4-quinolyl)oxyphenyl)-N'-(4-fluorophenyl)urea

HRID 387722Notes

Reaction equation

HRID 387722 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[OH:13])[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[O:23])=[CH:17][CH:16]=1)#[N:2].Br[CH2:33][CH2:34][Cl:35].C(=O)([O-])[O-].[K+].[K+].O1CCCC1>CN(C)C=O.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:33][CH2:34][Cl:35])[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[CH:16]=[CH:17][C:18]([NH:21][C:22]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)=[O:23])=[CH:19][CH:20]=1)#[N:2]

Participants

7

Reactant 4

HCID 78491-Bromo-2-ChloroethaneHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 135829395N-(4-(6-Cyano-7-hydroxy-4-quinolyl)oxyphenyl)-N'-(4-fluorophenyl)urea

Product 1

HCID 22936803N-(4-(6-Cyano-7-(2-chloroethoxy)-4-quinolyl)oxyphenyl)-N'-(4-fluorophenyl)ureaYield 75.72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

N-(4-(6-Cyano-7-hydroxy-4-quinolyl)oxyphenyl)-N′-(4-fluorophenyl)urea (400 mg, 0.9166 mmol) was dissolved in dimethylformamide (5.0 ml), and then 1-bromo-2-chloroethane (0.12 ml, 1.4479 mmol) and potassium carbonate (200 mg, 1.4479 mmol) were added and the mixture was heated and stirred at 55° C. for 4 hours. After cooling, tetrahydrofuran and ethyl acetate were added, the mixture was washed with saturated saline and dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to NH silica gel column chromatography (ethyl acetate-methanol system). The obtained crystals were suspended in diethyl ether, the suspension was diluted with hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (331 mg, 0.6941 mmol, 75.72%) as light yellow crystals.

Workup

  1. temperaturethe mixture was heated
  2. temperatureAfter cooling
  3. washthe mixture was washed with saturated saline
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. additionthe suspension was diluted with hexane
  7. filtrationthe crystals were filtered out
  8. washwashed with hexane
  9. customdried by aspiration

Sources & evidence

ORD record
ord-7f565117d51e4d528f0b497de11851f2
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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