7-(Benzyloxy)-4-chloro-6-methoxyquinoline → HCID 67072137, compound

HRID 1510103Notes

Reaction equation

HRID 1510103 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH3:22][O:23][C:24]([O:38][CH3:39])([CH3:37])[CH2:25][C:26]1[C:27]([F:36])=[C:28]([OH:35])[CH:29]=[CH:30][C:31]=1[N+:32]([O-:34])=[O:33]>O1CCOCC1.CCOC(C)=O.O>[CH2:15]([O:14][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([O:35][C:28]3[CH:29]=[CH:30][C:31]([N+:32]([O-:34])=[O:33])=[C:26]([CH2:25][C:24]([O:23][CH3:22])([O:38][CH3:39])[CH3:37])[C:27]=3[F:36])=[CH:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[O:12][CH3:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 2

HCID 226465627-(Benzyloxy)-4-chloro-6-methoxyquinolineHCID 67072177HCID 67072177, compound

Product 1

HCID 67072137HCID 67072137, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

4-Chloro-7-benzyloxy-6-methoxy-quinoline (WO2008112407, 1.5 g) was mixed with 3-(2,2-dimethoxypropyl)-2-fluoro-4-nitrophenol (WO0047212) (1.5 eq) in dioxane (30 ml). The reaction was refluxed for three days and diluted with EtOAc, water and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried. The solution was evaporated and purified with silica gel column to give 7-(benzyloxy)-4-(3-(2,2-dimethoxypropyl)-2-fluoro-4-nitrophenoxy)-6-methoxyquinoline (650 mg). This product was mixed with 2NHCl (3 ml) and acetone (30 ml) and refluxed for 6 hours. The reaction was diluted with EtOAc and neutralized with saturated NaHCO3, further extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried. The solution was evaporated and purified with silica gel column to give 1-(3-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-2-fluoro-6-nitrophenyl)propan-2-one (500 mg) which was mixed with iron (500 mg) and NH4Cl (50 mg) in EtOH/H2O (20 ml, 4/1). The reaction was refluxed for 4 hours, filter through Celite and evaporated. The residue was extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried. The solution was evaporated and purified with silica gel column to give 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-benzyloxyquinoline (250 mg).

Workup

  1. temperatureThe reaction was refluxed for three days
  2. extractionextracted with EtOAc three times
  3. washThe combined organic layer was washed with water, brine
  4. customdried
  5. customThe solution was evaporated
  6. custompurified with silica gel column

Sources & evidence

ORD record
ord-f573e722d31b4d5187db05f5c993c827
Source dataset
uspto-grants-2012_07
Patent number
US08211911B2

Reaction notes

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