4-Toluenesulfonyl chloride → 3-{4-amino-2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylpropanamide

HRID 244842Notes

Reaction equation

HRID 244842 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:25][CH2:26][CH2:27][N:28]2[CH2:32][CH2:31][CH2:30][C:29]2=[O:33])[C:7]2[C:16]3[CH:15]=[C:14]([CH2:17][CH2:18][C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:24]=1.ClC1C=C(C=CC=1)C(OO)=O.[OH-].[NH4+:46].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>ClCCl>[NH2:46][C:9]1[C:8]2[N:24]=[C:5]([CH2:4][CH2:3][O:2][CH3:1])[N:6]([CH2:25][CH2:26][CH2:27][N:28]3[CH2:32][CH2:31][CH2:30][C:29]3=[O:33])[C:7]=2[C:16]2[CH:15]=[C:14]([CH2:17][CH2:18][C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH:13]=[CH:12][C:11]=2[N:10]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 690823003-{2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylpropanamide

Product 1

HCID 576572703-{4-amino-2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylpropanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of 3-{2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylpropanamide, (0.66 g) in dichloromethane (75 mL) was added 3-chloroperoxybenzoic acid (60% pure, 423 mg, 1.62 mmol). After 18 hours concentrated ammonium hydroxide (50 mL) was added and the reaction was vigorously stirred for 10 minutes. p-Toluenesulfonyl chloride (311 mg, 1.62 mmol) was then added in one portion. The fractions were separated and aqueous fraction was extracted with chloroform (3×50 mL). The combined organic fractions were concentrated under reduced pressure and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a 0-30% gradient of CMA in chloroform). The resulting product was washed with a 1% aqueous sodium carbonate and then recrystallized from acetonitrile to provide 75 mg of 3-{4-amino-2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylpropanamide as an off-white solid, mp 184-186° C.

Workup

  1. customThe fractions were separated
  2. extractionaqueous fraction was extracted with chloroform (3×50 mL)
  3. concentrationThe combined organic fractions were concentrated under reduced pressure
  4. custompurified by chromatography
  5. washeluting with a 0-30% gradient of CMA in chloroform)
  6. washThe resulting product was washed with a 1% aqueous sodium carbonate
  7. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-5e4042f63f1b4d43a1b9db1368deb1fe
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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