3-Methoxypropanoyl chloride → tert-Butyl 4-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butylcarbamate

HRID 81880Notes

Reaction equation

HRID 81880 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C:5](Cl)=O.[NH2:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[NH:19][CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:16][CH:15]=[CH:14][CH:13]=2.Cl.N1C=CC=CC=1>N1C=CC=CC=1>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:19]([CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[C:18]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[CH:10][C:9]=2[N:8]=1

Participants

5

Reactant 3

HCID 27597283-Methoxypropanoyl chlorideHCID 10176127Pyridinium chlorideHCID 18783942tert-Butyl (4-((3-aminoquinolin-4-yl)amino)butyl)carbamate

Product 1

HCID 22381767tert-Butyl 4-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butylcarbamate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

3-Methoxypropionyl chloride (15.4 g, 126 mmol) was added dropwise over a period of 20 minutes to a chilled (ice bath) solution of tert-butyl N-{4-[(3-aminoquinolin-4-yl)amino]butyl}carbamate (38 g, 115 mmol, U.S. Pat. No. 6,541,485, Example 2, Part B) in pyridine. The reaction mixture was stirred for 4 hours and then allowed to stand at ambient temperature over the weekend. Pyridine hydrochloride (3.9 g, 34 mmol) was added and the reaction mixture was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure and the residue was diluted with dichloromethane (250 mL) and aqueous sodium bicarbonate (250 mL). The layers were separated. The separatory funnel was rinsed with a small amount of methanol to remove a residue coating the walls. The combined organics were concentrated under reduced pressure. The residue was purified by prep HPLC (COMBIFLASH system eluting first with a gradient of 0 to 5% methanol in dichloromethane containing 1% ammonium hydroxide and then with a gradient of 5 to 10% methanol in dichloromethane containing 1% ammonium hydroxide) to provide 18 g of tert-butyl N-{4-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}carbamate.

Workup

  1. customto stand at ambient temperature over the weekend
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux overnight
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additionthe residue was diluted with dichloromethane (250 mL) and aqueous sodium bicarbonate (250 mL)
  6. customThe layers were separated
  7. washThe separatory funnel was rinsed with a small amount of methanol
  8. customto remove a residue coating the walls
  9. concentrationThe combined organics were concentrated under reduced pressure
  10. customThe residue was purified by prep HPLC (COMBIFLASH system
  11. washeluting first with a gradient of 0 to 5% methanol in dichloromethane containing 1% ammonium hydroxide

Sources & evidence

ORD record
ord-35faa468c3224f36808cb8e41cb4c012
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Reaction notes

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