Ammonium Hydroxide → 8-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

HRID 2203622Notes

Reaction equation

HRID 2203622 reaction equation
C1C=C(Cl)C=C(C(OO)=O)C=1.[CH2:12]([O:19][C:20]1[CH:29]=[CH:28][C:27]2[N:26]=[CH:25][C:24]3[N:30]=[C:31]([CH2:36][O:37][CH2:38][CH3:39])[N:32]([CH2:33][CH2:34][CH3:35])[C:23]=3[C:22]=2[CH:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.ClC(Cl)(Cl)C([N:44]=C=O)=O.[OH-].[NH4+]>ClCCl>[CH2:12]([O:19][C:20]1[CH:29]=[CH:28][C:27]2[N:26]=[C:25]([NH2:44])[C:24]3[N:30]=[C:31]([CH2:36][O:37][CH2:38][CH3:39])[N:32]([CH2:33][CH2:34][CH3:35])[C:23]=3[C:22]=2[CH:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 76400Trichloroacetyl isocyanateHCID 670511278-benzyloxy-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinoline

Product 1

HCID 575453188-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

mCPBA (60% pure, 27.5 g, 95.9 mmol) was added in small portions over a period of 20 minutes to 8-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinoline (30.0 g, 79.9 mmol, prepared in Parts A through H of Example 2) in dichloromethane (400 mL). After the reaction was stirred for two hours, it was washed with 1% aqueous sodium carbonate (3×100 mL). The combined aqueous washings were extracted with chloroform (200 mL), and the combined organic fractions were dried over magnesium sulfate and filtered. Trichloroacetyl isocyanate (18.0 g, 95.9 mmol) was added dropwise to the filtrate, and then the reaction was stirred overnight at ambient temperature. Concentrated ammonium hydroxide (100 mL) was slowly added, and the mixture was stirred at ambient temperature for 30 minutes. The organic layer was separated and washed with 1% aqueous sodium carbonate (2×100 mL). The combined aqueous fractions were extracted with chloroform (3×75 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to yield a dark semi-solid. The crude product was purified on silica gel (1 kg, eluting sequentially with 2% methanol in chloroform and 5% methanol in chloroform) to provide 22 g of 8-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine as an off-white solid.

Workup

  1. washit was washed with 1% aqueous sodium carbonate (3×100 mL)
  2. extractionThe combined aqueous washings were extracted with chloroform (200 mL)
  3. dry with materialthe combined organic fractions were dried over magnesium sulfate
  4. filtrationfiltered
  5. stirringthe reaction was stirred overnight at ambient temperature
  6. stirringthe mixture was stirred at ambient temperature for 30 minutes
  7. customThe organic layer was separated
  8. washwashed with 1% aqueous sodium carbonate (2×100 mL)
  9. extractionThe combined aqueous fractions were extracted with chloroform (3×75 mL)
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto yield a dark semi-solid
  14. customThe crude product was purified on silica gel (1 kg
  15. washeluting sequentially with 2% methanol in chloroform and 5% methanol in chloroform)

Sources & evidence

ORD record
ord-ade131a2d70d4977b24db2ba6e7885a7
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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