4-Toluenesulfonyl chloride → N-[4-amino-2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-8-yl]-2-methylpropanamide

HRID 244864Notes

Reaction equation

HRID 244864 reaction equation
ClC1C=C(C=CC=1)C(OO)=O.[CH2:12]([O:14][CH2:15][C:16]1[N:17]([CH2:35][C:36]([OH:39])([CH3:38])[CH3:37])[C:18]2[C:27]3[CH:26]=[C:25]([NH:28][C:29](=[O:33])[CH:30]([CH3:32])[CH3:31])[CH:24]=[CH:23][C:22]=3[N:21]=[CH:20][C:19]=2[N:34]=1)[CH3:13].[OH-].[NH4+:41].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[NH2:41][C:20]1[C:19]2[N:34]=[C:16]([CH2:15][O:14][CH2:12][CH3:13])[N:17]([CH2:35][C:36]([OH:39])([CH3:37])[CH3:38])[C:18]=2[C:27]2[CH:26]=[C:25]([NH:28][C:29](=[O:33])[CH:30]([CH3:31])[CH3:32])[CH:24]=[CH:23][C:22]=2[N:21]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 69077219N-[2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-8-yl]-2-methylpropanamide

Product 1

HCID 57657238N-[4-amino-2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-8-yl]-2-methylpropanamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

3-Chloroperoxybenzoic acid (60% pure, 0.283 g, 1.0 mmol) was added to a solution of N-[2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-8-yl]-2-methylpropanamide (0.380 g, 1.0 mmol) in chloroform (10 mL) and the reaction was stirred for 1 hour. The mixture was cooled in an ice bath and ammonium hydroxide (3 mL) was added. After 15 minutes of stirring, p-toluenesulfonyl chloride (0.190 g, 1.0 mmol) was added and the reaction mixture was stirred for 72 hours. The fractions were separated and the aqueous fraction was extracted with chloroform. The combined organic fractions were washed with brine and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a linear gradient of 2-20% CMA in chloroform). Recrystallization from acetonitrile provided 0.231 g of N-[4-amino-2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-8-yl]-2-methylpropanamide as an off-white solid, mp 259-261° C.

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. stirringAfter 15 minutes of stirring
  3. stirringthe reaction mixture was stirred for 72 hours
  4. customThe fractions were separated
  5. extractionthe aqueous fraction was extracted with chloroform
  6. washThe combined organic fractions were washed with brine
  7. custompurified by chromatography
  8. washeluting with a linear gradient of 2-20% CMA in chloroform)
  9. customRecrystallization from acetonitrile

Sources & evidence

ORD record
ord-f8a6b5cbb6b64915903855bdcfe78e0e
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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