Sodium Carbonate → 4-(4-Chloro-2-fluoro-5-hydroxy-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile

HRID 612158Notes

Reaction equation

HRID 612158 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([O:14][CH3:15])[CH:8]=[CH:9][C:10]=2[O:12][CH3:13])[N:5]=[CH:4][C:3]=1[C:16]#[N:17].C(=O)([O-])OC.[Cl:23][C:24]1[C:30]([OH:31])=[CH:29][C:27]([NH2:28])=[C:26]([F:32])[CH:25]=1.C(OC(O)C)C.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[NH4+]>CO.CC(C)=O.O>[Cl:23][C:24]1[C:30]([OH:31])=[CH:29][C:27]([NH:28][C:2]2[C:11]3[C:6](=[C:7]([O:14][CH3:15])[CH:8]=[CH:9][C:10]=3[O:12][CH3:13])[N:5]=[CH:4][C:3]=2[C:16]#[N:17])=[C:26]([F:32])[CH:25]=1

Participants

10

Reactant 6

HCID 10340Sodium CarbonateHCID 14923Ammonium HydroxideHCID 1586545-Amino-2-chloro-4-fluorophenolHCID 4585885MethylcarbonateHCID 101298981-EthoxyethanolHCID 224665354-Chloro-5,8-dimethoxyquinoline-3-carbonitrile

Product 1

HCID 224666204-(4-Chloro-2-fluoro-5-hydroxy-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 0.223 g of 4-chloro-5,8-dimethoxy-3-quinolinecarbonitrile, 0.22 g of the methyl carbonate of 4-chloro-2-fluoro-5-hydroxy-aniline, and 15 ml of ethoxyethanol was stirred under nitrogen, at reflux temperature for 30 minutes. The mixture was cooled and added to 100 ml of water. To this mixture was added sodium carbonate to pH 9. The product was collected, washed with water, and dried. The solids thus obtained were dissolved in a mixture of 30 ml of methyl alcohol and 20 ml of acetone. To this mixture was added 1.5 ml of 28-30% ammonium hydroxide solution. The mixture was heated at 50° C. for 30 minutes and concentrated. The product was collected, washed with ethyl acetate, and dried to give 0.237 g of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile as a solid, mp 240° C. (decomposed); mass spectrum (electrospray, m/e): M+H 373.9.

Workup

  1. temperatureat reflux temperature for 30 minutes
  2. temperatureThe mixture was cooled
  3. customThe product was collected
  4. washwashed with water
  5. customdried
  6. customThe solids thus obtained
  7. concentrationconcentrated
  8. customThe product was collected
  9. washwashed with ethyl acetate
  10. customdried

Sources & evidence

ORD record
ord-e8831f0ef872437587e3e4a6440415bb
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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