Thioanisole → N-(4-((6-Cyano-7-hydroxy-4-quinolyl)oxy)phenyl)-N'-(3-(methylsulfonyl)phenyl)urea

HRID 1010110Notes

Reaction equation

HRID 1010110 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([S:36]([CH3:39])(=[O:38])=[O:37])[CH:31]=4)=[O:28])=[CH:22][CH:21]=3)=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[C:40]#[N:41])C1C=CC=CC=1.C1(SC)C=CC=CC=1>FC(F)(F)C(O)=O.C(OCC)(=O)C>[C:40]([C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][C:9]=1[OH:8])[N:16]=[CH:15][CH:14]=[C:13]2[O:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([S:36]([CH3:39])(=[O:38])=[O:37])[CH:31]=2)=[O:28])=[CH:22][CH:21]=1)#[N:41]

Participants

5

Reactant 2

HCID 7520ThioanisoleHCID 22936455N-(4-(7-(Benzyloxy)-6-cyano-4-quinolyl)oxyphenyl)-N'-(3-(methylsulfonyl)phenyl)urea

Product 1

HCID 135829382N-(4-((6-Cyano-7-hydroxy-4-quinolyl)oxy)phenyl)-N'-(3-(methylsulfonyl)phenyl)ureaYield 72.7%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

After dissolving N-(4-(7-(benzyloxy)-6-cyano-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea (1.43 g, 2.5 mmol) in trifluoroacetic acid (10 ml) and thioanisole (1.17 ml, 10 mmol) under a nitrogen atmosphere, the solution was stirred at 65° C. for 19 hours. The reaction solution was concentrated under reduced pressure, and after adding 5% aqueous sodium bicarbonate (30 ml) and ethyl acetate (50 ml) to the obtained residue and stirring, the precipitated crystals were filtered out, washed with water and ethyl acetate and dried under reduced pressure. The organic layer of the filtrate was separated, washed with saturated brine and dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain a yellow crystalline residue. This was combined with the previous crystals, suspended in ethyl acetate (40 ml) and subjected to sonication, and then the crystals were filtered out, washed with diethyl ether and dried at 60° C. to obtain the title compound (862 mg, 1.8 mmol, 72.7%) as yellow crystals.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additionafter adding 5% aqueous sodium bicarbonate (30 ml) and ethyl acetate (50 ml) to the obtained residue
  3. stirringstirring
  4. filtrationthe precipitated crystals were filtered out
  5. washwashed with water and ethyl acetate
  6. customdried under reduced pressure
  7. customThe organic layer of the filtrate was separated
  8. washwashed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customto obtain a yellow crystalline residue
  12. customsubjected to sonication
  13. filtrationthe crystals were filtered out
  14. washwashed with diethyl ether
  15. customdried at 60° C.

Sources & evidence

ORD record
ord-457f47290ed0497ca617cc6f8f06fca1
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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