Sodium Hydroxide → N-[2-(4-amino-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-yloxy)ethyl]methanesulfonamide

HRID 540817Notes

Reaction equation

HRID 540817 reaction equation
[CH3:1][S:2]([O:5]S(C)(=O)=O)(=O)=[O:3].[NH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:23]=[CH:22][C:21]2[N:20]=[C:19]([NH2:24])[C:18]3[N:25]=[C:26]([CH2:31][O:32][CH2:33][CH3:34])[N:27]([CH2:28][CH2:29][CH3:30])[C:17]=3[C:16]=2[CH:15]=1.[OH-].[Na+]>ClCCl>[NH2:24][C:19]1[C:18]2[N:25]=[C:26]([CH2:31][O:32][CH2:33][CH3:34])[N:27]([CH2:28][CH2:29][CH3:30])[C:17]=2[C:16]2[CH:15]=[C:14]([O:13][CH2:12][CH2:11][NH:10][S:2]([CH3:1])(=[O:5])=[O:3])[CH:23]=[CH:22][C:21]=2[N:20]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 81560Methanesulfonic anhydrideHCID 588336918-(2-aminoethoxy)-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 58833634N-[2-(4-amino-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-yloxy)ethyl]methanesulfonamideYield 49.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonic anhydride (0.265 g, 1.52 mmol) was added in one portion to a solution of 8-(2-aminoethoxy)-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine (0.500 g, 1.46 mmol) in dichloromethane (10 mL), and the reaction was stirred for 30 minutes. A precipitate formed. Aqueous sodium hydroxide (25 mL of 10%) was added, and the mixture was stirred for 20 minutes. The aqueous layer was separated and extracted with dichloromethane. The combined organic fractions were washed sequentially with water and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting white solid was purified by column chromatography on silica gel (eluting with a dichloromethane:methanol ranging in ratios from 97:3 to 94:6) and then recrystallized from acetonitrile to yield 0.302 g of N-[2-(4-amino-2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-yloxy)ethyl]methanesulfonamide as white, granular crystals, mp 178-179.5° C.

Workup

  1. customA precipitate formed
  2. stirringthe mixture was stirred for 20 minutes
  3. customThe aqueous layer was separated
  4. extractionextracted with dichloromethane
  5. washThe combined organic fractions were washed sequentially with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting white solid was purified by column chromatography on silica gel (
  10. washeluting with a dichloromethane
  11. custommethanol ranging in ratios from 97:3 to 94:6) and then recrystallized from acetonitrile

Sources & evidence

ORD record
ord-5fd6efa7cc614dd389893b67a7091e9d
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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