Sodium Carbonate → 4-(4-Chloro-2-fluoro-phenylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrile

HRID 612150Notes

Reaction equation

HRID 612150 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([O:16][CH3:17])[C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:18]#[N:19].[Cl:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[C:23]([F:28])[CH:22]=1.C(OC(O)C)C.C(=O)([O-])[O-].[Na+].[Na+]>O>[Cl:20][C:21]1[CH:27]=[CH:26][C:24]([NH:25][C:2]2[C:11]3[C:6](=[C:7]([O:16][CH3:17])[C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:18]#[N:19])=[C:23]([F:28])[CH:22]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 938984-Chloro-2-fluoroanilineHCID 101298981-EthoxyethanolHCID 224666114-Chloro-6,7,8-trimethoxy-3-quinolinecarbonitrile

Product 1

HCID 224667464-(4-Chloro-2-fluoro-phenylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrileYield 67.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 0.279 g of 4-chloro-6,7,8-trimethoxy-quinoline-3-carbonitrile, 0.177 g of 4-chloro-2-fluoroaniline, and 10 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 extracted with ethyl acetate, washed with water, dried and concentrated in vacuo. The solid thus obtained was chromatographed on silica gel eluting with hexanes-ethyl acetate 9:1 to 2:1. Solvent was removed from product fractions giving 0.261 g of 4-(4-chloro-2-fluoro-phenylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrile as a yellow solid: mp 166-168° C.; mass spectrum (EI, m/e): M 387.0777.

Workup

  1. temperatureat reflux temperature for 30 minutes
  2. temperatureThe mixture was cooled
  3. extractionThe product was extracted with ethyl acetate
  4. washwashed with water
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe solid thus obtained
  8. customwas chromatographed on silica gel eluting with hexanes-ethyl acetate 9:1 to 2:1
  9. customSolvent was removed from product fractions

Sources & evidence

ORD record
ord-b75b67f8db2c4faba54ee2b83c66bffe
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

Loading…