Methanesulfonic anhydride → N-{3-[4-amino-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-7-yloxy]propyl}methanesulfonamide

HRID 540825Notes

Reaction equation

HRID 540825 reaction equation
[CH3:1][S:2]([O:5]S(C)(=O)=O)(=O)=[O:3].[NH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]2[C:19]3[N:28]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:27]([CH2:33][CH2:34][CH3:35])=[N:26][C:20]=3[C:21]([NH2:25])=[N:22][C:23]=2[CH:24]=1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[NH2:25][C:21]1[C:20]2[N:26]=[C:27]([CH2:33][CH2:34][CH3:35])[N:28]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:19]=2[C:18]2[CH:17]=[CH:16][C:15]([O:14][CH2:13][CH2:12][CH2:11][NH:10][S:2]([CH3:1])(=[O:5])=[O:3])=[CH:24][C:23]=2[N:22]=1

Participants

5

Reactant 3

HCID 81560Methanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 588337127-(3-aminopropoxy)-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 58833704N-{3-[4-amino-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-7-yloxy]propyl}methanesulfonamideYield 26.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonic anhydride (0.245 g, 1.41 mmol) was added in one portion to a suspension of 7-(3-aminopropoxy)-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine (0.500 g, 1.41 mmol) in chloroform, and the reaction was stirred for 18 hours. Saturated aqueous sodium bicarbonate was added, and the reaction was stirred for 20 minutes. The aqueous layer was separated and extracted with chloroform. The combined organic fractions were washed with water and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting off-white solid was dissolved in concentrated hydrochloric acid; the solution was then cooled to 0° C. and adjusted to pH 13 with the addition of 50% aqueous sodium hydroxide. The opaque solution was extracted with dichloromethane. The extract was washed sequentially with water and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid was recrystallized from acetonitrile to yield 0.160 g of N-{3-[4-amino-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-7-yloxy]propyl}methanesulfonamide as a flocculent, white solid, mp 166.5-168.5° C.

Workup

  1. stirringthe reaction was stirred for 20 minutes
  2. customThe aqueous layer was separated
  3. extractionextracted with chloroform
  4. washThe combined organic fractions were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe resulting off-white solid was dissolved in concentrated hydrochloric acid
  9. additionadjusted to pH 13 with the addition of 50% aqueous sodium hydroxide
  10. extractionThe opaque solution was extracted with dichloromethane
  11. washThe extract was washed sequentially with water and brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe resulting solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-f4f6488b3f4c4d6c86be5cd5e4108d3f
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

Loading…