Ethyl 2-chloroethanecarboximidate hydrochloride → ethyl 3-[2-(chloromethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanoate

HRID 221564Notes

Reaction equation

HRID 221564 reaction equation
Cl.[Cl:2][CH2:3][C:4](=N)OCC.[NH2:9][C:10]1[CH:11]=[N:12][C:13]2[C:18]([C:19]=1[NH:20][CH:21]([CH3:28])[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:17][CH:16]=[CH:15][CH:14]=2>C(Cl)(Cl)Cl>[Cl:2][CH2:3][C:4]1[N:20]([CH:21]([CH3:28])[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:19]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[CH:11][C:10]=2[N:9]=1

Participants

4

Reactant 2

HCID 12470659Ethyl 2-chloroethanecarboximidate hydrochloride2×HCID 67156698Ethyl 3-[(3-aminoquinolin-4-yl)amino]butanoate

Product 1

HCID 67157300ethyl 3-[2-(chloromethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanoateYield 97.7%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

Ethyl 2-chloroethanimidoate hydrochloride (10.8 g, 68.4 mmol) was added to a solution of ethyl 3-[(3-aminoquinolin-4-yl)amino]butanoate (9.41 g, 34.4 mmol) in chloroform (130 mL), and the reaction was stirred at room temperature for three days and then heated at reflux for two hours. An analysis by liquid chromatography/mass spectrometry (LC/MS) indicated the presence of starting material, and additional ethyl 2-chloroethanimidoate hydrochloride (2.7 g) was added. The reaction was heated at reflux for an additional 1.5 hours, allowed to cool to room temperature, diluted with chloroform (100 mL), washed sequentially with brine (2×150 mL) and deionized water (100 mL), dried over magnesium sulfate, filtered through a layer of CELITE filter agent, concentrated under reduced pressure, and further dried overnight under high vacuum to provide 11.15 g of ethyl 3-[2-(chloromethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanoate as a dark yellow solid.

Workup

  1. temperatureheated
  2. temperatureat reflux for two hours
  3. additionwas added
  4. temperatureThe reaction was heated
  5. temperatureat reflux for an additional 1.5 hours
  6. temperatureto cool to room temperature
  7. washwashed sequentially with brine (2×150 mL) and deionized water (100 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered through a layer of CELITE filter agent
  10. concentrationconcentrated under reduced pressure
  11. customfurther dried overnight under high vacuum

Sources & evidence

ORD record
ord-f56251d52a104fe38add97befc94d60c
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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