7-Benzyloxy-4-chloro-6-cyanoquinoline → N-(4-(6-Cyano-7-benzyloxy-4-quinolyl)oxy-2-fluorophenyl)-N'-(2,4-difluorophenyl)urea

HRID 387719Notes

Reaction equation

HRID 387719 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:14]=1[F:20])=[O:11].Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[C:29]([C:32]#[N:33])[CH:30]=2)[N:25]=[CH:24][CH:23]=1>>[C:32]([C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][C:28]=1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[N:25]=[CH:24][CH:23]=[C:22]2[O:19][C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[O:11])=[C:14]([F:20])[CH:15]=1)#[N:33]

Participants

3

Reactant 2

HCID 226465197-Benzyloxy-4-chloro-6-cyanoquinolineHCID 22936983N-(2,4-Difluorophenyl)-N'-(2-fluoro-4-hydroxyphenyl)urea

Product 1

HCID 22936621N-(4-(6-Cyano-7-benzyloxy-4-quinolyl)oxy-2-fluorophenyl)-N'-(2,4-difluorophenyl)ureaYield 16.1%

Procedure

N-(2,4-Difluorophenyl)-N′-(2-fluoro-4-hydroxyphenyl)urea (227 mg, 0.8058 mmol) and 4-chloro-6-cyano-7-benzyloxyquinoline (250 mmol, 0.8482 mmol) were used for reaction in the same manner as the second method in Example 86, and after cooling, extraction and washing with water, the solvent was distilled off under reduced pressure and the obtained crystals were suspended in diethyl ether, washed and filtered. They were then dissolved in tetrahydrofuran and filtered with silica gel, and the solvent was distilled off under reduced pressure. These crystals were then suspended in diethyl ether, washed with water and filtered, and then washed with diethyl ether and dried by aspiration to obtain the title compound (70 mg, 0.1295 mmol, 16.07%) as light brown crystals.

Workup

  1. temperatureafter cooling
  2. extractionextraction
  3. washwashing with water
  4. distillationthe solvent was distilled off under reduced pressure
  5. washwashed
  6. filtrationfiltered
  7. dissolutionThey were then dissolved in tetrahydrofuran
  8. filtrationfiltered with silica gel
  9. distillationthe solvent was distilled off under reduced pressure
  10. washwashed with water
  11. filtrationfiltered
  12. washwashed with diethyl ether
  13. customdried by aspiration

Sources & evidence

ORD record
ord-902d592dfdfd414c85f287f7d567f5c5
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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