1,4-Cyclohexadiene → N-(3-Fluoro-4-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 445463Notes

Reaction equation

HRID 445463 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([O:36]CC6C=CC=CC=6)=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][CH:25]=4)=[C:19]([F:44])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.C1CC=CCC=1>CCO.[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][CH:25]=4)=[C:19]([F:44])[CH:18]=3)=[O:15])[CH2:12][CH2:13]2)=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 57810139N-[3-Fluoro-4-[[6-methoxy-7-(phenylmethoxy)-4-quinolinyl]oxy]phenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide

Product 1

HCID 136168657N-(3-Fluoro-4-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 89%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of cyclopropane-1,1-dicarboxylic acid [4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide (4-fluoro-phenyl)-amide (1.18 g, 2.0 mmol) in EtOH (20 mL) was added 1,4-cyclohexadiene (2.0 mL, 20 mmol) and 10% Pd/C (300 mg). The reaction mixture was then heated to reflux and the stirring was continued for 2 h. It was cooled to room temperature, filtered through celite and washed with MeOH. The MeOH solution was then concentrated under reduced pressure. The residue was taken into EtOAc (200 mL). The EtOAc solution washed with water, and dried over Na2SO4. Removal of the solvent under reduced pressure gave 900 mg (89%) of the crude product (90% purity by analytical HPLC), which was used in the next reaction without further purification.

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureto reflux
  3. filtrationfiltered through celite
  4. washwashed with MeOH
  5. concentrationThe MeOH solution was then concentrated under reduced pressure
  6. washThe EtOAc solution washed with water
  7. dry with materialdried over Na2SO4
  8. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-158dd38944334d05b9da1a54f93429a6
Source dataset
uspto-grants-2013_07
Patent number
US08476298B2

Reaction notes

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