O-Toluidine → 3-(3-(Ethoxycarbonyl)propionyl)-8-methoxy-4-((2-methylphenyl)amino)quinoline

HRID 2379427Notes

Reaction equation

HRID 2379427 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([O:12][CH3:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:22])[CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].[NH2:23][C:24]1[C:25]([CH3:30])=[CH:26][CH:27]=[CH:28][CH:29]=1>O1CCCC1>[CH2:20]([O:19][C:17]([CH2:16][CH2:15][C:14]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH3:30])=[CH:10][CH:9]=[CH:8][C:7]=2[O:12][CH3:13])=[O:22])=[O:18])[CH3:21]

Participants

4

Reactant 2

HCID 7242O-ToluidineHCID 14956373HCID 14956373, compound

Product 1

HCID 1924943-(3-(Ethoxycarbonyl)propionyl)-8-methoxy-4-((2-methylphenyl)amino)quinolineYield 83.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

In a flame-dried, three-necked round-bottomed reaction flask equipped with reflux condenser, magnetic stirring bar and addition funnel, there were placed 1.72 g (0.00535 mole) of 4-chloro-3-(3-ethoxycarbonylpropionyl)-8-methoxyquinoline (the product of Preparation C) dissolved in 15 mL of dry tetrahydrofuran. Stirring was commenced and the resulting organic solution was then treated dropwise with a solution consisting of 573 mg (0.00535 mole) of o-toluidine (available from the Aldrich Chemical Company, Inc. of Milwaukee, Wis.) dissolved in 15 mL of dry tetrahydrofuran. The resulting reaction mixture was then stirred and heated to 60° C. and thereafter kept at that temperature for a period of approximately 16 hours (i.e., overnight). Upon completion of this step, the final reaction mixture was slowly allowed to cool to ambient temperatures (ca. 20° C.) and the yellow precipitate which resulted was subsequently collected by means of suction filtration and air-dried on the filter funnel to constant weight. Recrystallization of the latter crude salt material from methylene chloride/ethyl acetate/petroleum ether then gave 1.75 g (76%) of pure 3-(3-ethoxycarbonylpropionyl)-8-methoxy-4-(2-methylphenylamino)quinoline as the hydrochloride salt, m.p. 210°-211° C. The pure product was further characterized by means of mass spectrum (MS) analysis and nuclear magnetic resonance (NMR) data, in addition to elemental analysis.

Workup

  1. customIn a flame-dried, three-necked round-bottomed reaction flask equipped
  2. temperaturewith reflux
  3. additioncondenser, magnetic stirring bar and addition funnel
  4. customthe product of Preparation C)
  5. additionthe resulting organic solution was then treated dropwise with a solution
  6. customThe resulting reaction mixture
  7. stirringwas then stirred
  8. custom(i.e., overnight)
  9. customUpon completion of this step, the final reaction mixture
  10. temperatureto cool to ambient temperatures (ca. 20° C.)
  11. customthe yellow precipitate which resulted
  12. filtrationwas subsequently collected by means of suction filtration
  13. customair-dried on the filter funnel to constant weight
  14. customRecrystallization of the latter crude salt material from methylene chloride/ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-c8c72cd109cd49d8af2bb9ed23064077
Source dataset
uspto-grants-1994_11
Patent number
US05362743

Reaction notes

Loading…