p-Toluenesulfonic acid → HCID 22672652, compound

HRID 1601697Notes

Reaction equation

HRID 1601697 reaction equation
[NH2:1][C:2]1[C:3]([Cl:18])=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][C:14]([OH:17])([CH3:16])[CH3:15])=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH2:19]([O:21][CH2:22][C:23](Cl)=O)[CH3:20].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(#N)C>[Cl:18][C:3]1[C:2]2[N:1]=[C:20]([CH2:19][O:21][CH2:22][CH3:23])[N:12]([CH2:13][C:14]([CH3:16])([CH3:15])[OH:17])[C:11]=2[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 84189Ethoxyacetyl chlorideHCID 226726541-((3-Amino-2-chloroquinolin-4-yl)amino)-2-methylpropan-2-ol

Product 1

HCID 22672652HCID 22672652, compoundYield 71.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-Amino-2-chloro-4-(2-hydroxy-2-methylpropylamino)quinoline (2.0 g, 7.5 mmol) was combined with acetonitrile (80 mL). Ethoxyacetyl chloride (0.92 g, 7.5 mmol) was added to the reaction mixture. After about 5 minutes a yellow precipitate formed. p-Toluenesulfonic acid (0.1 g) was added and the reaction mixture was heated to reflux. Refluxing was continued for about 120 hours at which time the reaction mixture was homogeneous. The reaction mixture was cooled and the acetonitrile was removed under vacuum. The resulting residue was dissolved in methylene chloride and washed with dilute ammonium hydroxide. The aqueous phase was extracted with methylene chloride (3×25 mL). The organic phases were combined, dried over magnesium sulfate and then concentrated to provide 2.6 g of crude product as a dark yellow solid. The crude product was recrystallized from t-butylmethyl ether to provide 1.8 g of a solid. The structure was confirmed by nuclear magnetic resonance spectroscopy.

Workup

  1. customAfter about 5 minutes a yellow precipitate formed
  2. temperaturethe reaction mixture was heated to reflux
  3. temperatureRefluxing
  4. temperatureThe reaction mixture was cooled
  5. customthe acetonitrile was removed under vacuum
  6. dissolutionThe resulting residue was dissolved in methylene chloride
  7. washwashed with dilute ammonium hydroxide
  8. extractionThe aqueous phase was extracted with methylene chloride (3×25 mL)
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated
  11. customto provide 2.6 g of crude product as a dark yellow solid
  12. customThe crude product was recrystallized from t-butylmethyl ether

Sources & evidence

ORD record
ord-a22dc518088b431e8c03f21f444f3e12
Source dataset
uspto-grants-1999_11
Patent number
US05977366

Reaction notes

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