Triethylamine → N-[2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]methanesulfonamide

HRID 540854Notes

Reaction equation

HRID 540854 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][C:14]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])([CH3:16])[CH3:15])=[CH:9][CH:8]=[C:7]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:6]=2.C(N(CC)CC)C.[CH2:37]([O:39][CH2:40][C:41](Cl)=O)[CH3:38]>ClCCl>[CH2:23]([O:22][C:7]1[CH:8]=[CH:9][C:10]2[C:11]3[N:12]([CH2:13][C:14]([NH:17][S:18]([CH3:21])(=[O:19])=[O:20])([CH3:16])[CH3:15])[C:38]([CH2:37][O:39][CH2:40][CH3:41])=[N:1][C:2]=3[CH:3]=[N:4][C:5]=2[CH:6]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 84189Ethoxyacetyl chlorideHCID 67050976N-[2-(3-amino-7-benzyloxyquinolin-4-ylamino)-1,1-dimethylethyl]methanesulfonamide

Product 1

HCID 67051174N-[2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]methanesulfonamideYield 84.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under a nitrogen atmosphere, a solution of N-[2-(3-amino-7-benzyloxyquinolin-4-ylamino)-1,1-dimethylethyl]methanesulfonamide (12.6 g, 30.4 mmol) in dichloromethane (300 mL) was cooled to ˜0° C.; triethylamine (4.23 mL, 30.4 mmol) was added. Ethoxy acetyl chloride (3.33 mL, 30.4 mmol) was added dropwise, and the reaction was stirred at ambient temperature for 1.5 hours. The volatiles were removed under reduced pressure, and the residue was dissolved in ethanol (300 mL). Triethylamine (13 mL) was added, and the reaction was heated at reflux overnight and allowed to cool to ambient temperature. The volatiles were removed under reduced pressure. The residue was dissolved in dichloromethane (300 mL), and the resulting solution was washed with water (2×100 mL) and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide a brown oil. The oil was purified by column chromatography on silica gel (eluting with 97.5:2.5 chloroform:methanol) to provide 12.4 g of N-[2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]methanesulfonamide as a beige solid.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. dissolutionthe residue was dissolved in ethanol (300 mL)
  3. additionTriethylamine (13 mL) was added
  4. temperaturethe reaction was heated
  5. temperatureat reflux overnight
  6. temperatureto cool to ambient temperature
  7. customThe volatiles were removed under reduced pressure
  8. dissolutionThe residue was dissolved in dichloromethane (300 mL)
  9. washthe resulting solution was washed with water (2×100 mL) and brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto provide a brown oil
  14. customThe oil was purified by column chromatography on silica gel (eluting with 97.5:2.5 chloroform:methanol)

Sources & evidence

ORD record
ord-7b2f8199ae3c40bea62264a5ac27729e
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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