4-Toluenesulfonyl chloride → 3-[4-amino-2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylpropanamide

HRID 244838Notes

Reaction equation

HRID 244838 reaction equation
[CH2:1]([C:3]1[N:4]([CH2:23][C:24]([OH:27])([CH3:26])[CH3:25])[C:5]2[C:14]3[CH:13]=[CH:12][C:11]([CH2:15][CH2:16][C:17]([N:19]([CH3:21])[CH3:20])=[O:18])=[CH:10][C:9]=3[N:8]=[CH:7][C:6]=2[N:22]=1)[CH3:2].ClC1C=C(C=CC=1)C(OO)=O.[OH-].[NH4+:40].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>ClCCl>[NH2:40][C:7]1[C:6]2[N:22]=[C:3]([CH2:1][CH3:2])[N:4]([CH2:23][C:24]([OH:27])([CH3:26])[CH3:25])[C:5]=2[C:14]2[CH:13]=[CH:12][C:11]([CH2:15][CH2:16][C:17]([N:19]([CH3:21])[CH3:20])=[O:18])=[CH:10][C:9]=2[N:8]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 690766703-[2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylpropanamide

Product 1

HCID 576572433-[4-amino-2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylpropanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of crude 3-[2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylpropanamide, (1.2 g, 3.3 mmol) in dichloromethane (75 mL) was added 3-chloroperoxybenzoic acid (60% pure, 941 mg, 3.6 mmol). After 18 hours concentrated ammonium hydroxide (50 mL) was added and the reaction was vigorously stirred for 10 minutes. p-Toluenesulfonyl chloride (690 mg, 3.6 mmol) was then added in one portion and the reaction was stirred for one hour. The fractions were separated and the aqueous fraction was extracted with chloroform (3×50 mL). The combined organic fractions were concentrated under reduced pressure. Purification of the residue by chromatography using a HORIZON HPFC system (silica cartridge, eluting with 0-6% gradient of methanol in dichloromethane) followed by recrystallization from acetonitrile provided 651 mg of 3-[4-amino-2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylpropanamide as an off-white solid, mp 234-237° C.

Workup

  1. stirringthe reaction was stirred for one hour
  2. customThe fractions were separated
  3. extractionthe aqueous fraction was extracted with chloroform (3×50 mL)
  4. concentrationThe combined organic fractions were concentrated under reduced pressure
  5. customPurification of the residue by chromatography
  6. washa HORIZON HPFC system (silica cartridge, eluting with 0-6% gradient of methanol in dichloromethane)
  7. customfollowed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-992bc94e5c784a17aa8882b8444ef83b
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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