Water → 7-[3-(1,1-dioxidoisothiazolidin-2-yl)propoxy]-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine

HRID 2203504Notes

Reaction equation

HRID 2203504 reaction equation
Cl[CH2:2][CH2:3][CH2:4][S:5](Cl)(=[O:7])=[O:6].[NH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:15]=[CH:16][C:17]2[C:18]3[N:27]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:26]([CH2:32][CH2:33][CH3:34])=[N:25][C:19]=3[C:20]([NH2:24])=[N:21][C:22]=2[CH:23]=1.N12CCCN=C1CCCCC2.O>C(Cl)(Cl)Cl>[O:6]=[S:5]1(=[O:7])[CH2:4][CH2:3][CH2:2][N:9]1[CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:15]=[CH:16][C:17]2[C:18]3[N:27]([CH2:28][CH:29]([CH3:30])[CH3:31])[C:26]([CH2:32][CH2:33][CH3:34])=[N:25][C:19]=3[C:20]([NH2:24])=[N:21][C:22]=2[CH:23]=1

Participants

6

Reactant 4

HCID 962WaterHCID 154103-Chloropropanesulphonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 588337127-(3-aminopropoxy)-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 588337267-[3-(1,1-dioxidoisothiazolidin-2-yl)propoxy]-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amineYield 36.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

3-Chloropropanesulfonyl chloride (0.206 mL, 1.69 mmol) was added dropwise 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 (17 mL), and the reaction was stirred for 30 minutes. The solvent was removed under reduced pressure, and the residue was dissolved in DMF (17 mL). 1,8-Diazabicyclo[5.4.0]undec-7-ene (0.316 mL, 2.11 mmol) was then added, and the reaction was stirred for 18 hours. The reaction was poured into water, and the mixture was extracted twice with dichloromethane. The combined organic fractions were washed sequentially with water and brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting with 97:3 dichloromethane:methanol) followed by recrystallization from acetonitrile to provide 0.237 g of 7-[3-(1,1-dioxidoisothiazolidin-2-yl)propoxy]-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine as needle-like, white crystals, mp 142-144° C.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (17 mL)
  3. stirringthe reaction was stirred for 18 hours
  4. extractionthe mixture was extracted twice with dichloromethane
  5. washThe combined organic fractions were washed sequentially with water and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (eluting with 97:3 dichloromethane:methanol)
  9. customfollowed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-bb85146f3fa944fc86a904c58fd75da6
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

Loading…