Triethylamine → N-(4-chloroquinolin-3-yl)-2-methylpropanamide

HRID 2105487Notes

Reaction equation

HRID 2105487 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[Cl:12])=[CH:9][CH:8]=[CH:7][CH:6]=2.C(N(CC)CC)C.[C:20](Cl)(=[O:24])[CH:21]([CH3:23])[CH3:22]>ClCCl.CO>[Cl:12][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[CH:3][C:2]=1[NH:1][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 62325Isobutyryl chloride3×HCID 8173324-chloroquinolin-3-amine

Product 1

HCID 67505834N-(4-chloroquinolin-3-yl)-2-methylpropanamideYield 80.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-amino-4-chloroquinoline (8.5 g, 48 mmol) in dichloromethane (100 mL) was cooled to 0° C. Triethylamine (42 mL, 0.30 mol) was added followed by a solution of isobutyryl chloride (9.6 mL, 0.10 mol) in dichloromethane (35 mL), which was added dropwise. The reaction was stirred overnight at room temperature. An analysis by LC/MS indicated the presence of starting material, and the reaction was heated at reflux for two hours. The reaction was still incomplete. The volatiles were removed under reduced pressure, and the residue was dissolved in dichloromethane (75 mL). Additional isobutyryl chloride (9.6 mL, 0.10 mol) was added, the reaction was stirred for three days at room temperature. The reaction was still incomplete, and additional isobutyryl chloride (3 mL) was added. The reaction was stirred overnight, diluted with methanol (10 mL), stirred for 30 minutes, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (150 mL), and the solution was washed with saturated aqueous sodium bicarbonate (3×50 mL), dried over potassium carbonate, filtered, and concentrated under reduced pressure to provide 9.6 g of N-(4-chloroquinolin-3-yl)-2-methylpropanamide as a brown solid.

Workup

  1. additionwas added dropwise
  2. temperaturethe reaction was heated
  3. temperatureat reflux for two hours
  4. customThe volatiles were removed under reduced pressure
  5. dissolutionthe residue was dissolved in dichloromethane (75 mL)
  6. stirringthe reaction was stirred for three days at room temperature
  7. stirringThe reaction was stirred overnight
  8. stirringstirred for 30 minutes
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was dissolved in dichloromethane (150 mL)
  11. washthe solution was washed with saturated aqueous sodium bicarbonate (3×50 mL)
  12. dry with materialdried over potassium carbonate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-744d85a44c714fe7995468b1d2588dd1
Source dataset
uspto-grants-2009_08
Patent number
US07579359B2

Reaction notes

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