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

HRID 244867Notes

Reaction equation

HRID 244867 reaction equation
[CH2:1]([C:3]1[N:4]([CH2:29][C:30]([OH:33])([CH3:32])[CH3:31])[C:5]2[C:14]3[CH:13]=[CH:12][C:11]([CH2:15][CH2:16][N:17]4[C:25](=[O:26])[C:24]5[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=5)[C:18]4=[O:27])=[CH:10][C:9]=3[N:8]=[CH:7][C:6]=2[N:28]=1)[CH3:2].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:7]1[C:6]2[N:28]=[C:3]([CH2:1][CH3:2])[N:4]([CH2:29][C:30]([OH:33])([CH3:32])[CH3:31])[C:5]=2[C:14]2[CH:13]=[CH:12][C:11]([CH2:15][CH2:16][N:17]3[C:25](=[O:26])[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]3=[O:27])=[CH:10][C:9]=2[N:8]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 690831192-{2-[2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]ethyl}-1H-isoindole-1,3(2H)-dione

Product 1

HCID 690831142-{2-[4-amino-2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]ethyl}-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-{2-[2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]ethyl}-1H-isoindole-1,3(2H)-dione (1.90 g, 4.29 mmol) in dichloromethane (75 mL) was combined with 3-chloroperoxybenzoic acid (60% pure, 1.24 g, 4.72 mmol) and the reaction was stirred for 18 hours. Concentrated ammonium hydroxide (40 mL) was added and the mixture was vigorously stirred for an additional 10 minutes. p-Toluenesulfonyl chloride (900 mg, 4.72 mmol) was added and the mixture was stirred for an additional 1 hour. The fractions were separated and the aqueous fraction was extracted with chloroform (3×50 mL). The combined organic fractions were sequentially dried (MgSO4), filtered, and concentrated under reduced pressure. Purification by chromatography using a HORIZON HPFC system (silica cartridge, eluting with 0-8% gradient of methanol in dichloromethane) provided 1.05 g of 2-{2-[4-amino-2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]ethyl}-1H-isoindole-1,3(2H)-dione as an off-white foam. MS (APCI) m/z 458 (M+H)+.

Workup

  1. stirringthe mixture was vigorously stirred for an additional 10 minutes
  2. stirringthe mixture was stirred for an additional 1 hour
  3. customThe fractions were separated
  4. extractionthe aqueous fraction was extracted with chloroform (3×50 mL)
  5. dry with materialThe combined organic fractions were sequentially dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by chromatography
  9. washa HORIZON HPFC system (silica cartridge, eluting with 0-8% gradient of methanol in dichloromethane)

Sources & evidence

ORD record
ord-737749bcd6344ce695289b82d0c4befd
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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