4-Toluenesulfonyl chloride → 7-benzyloxy-1-[(2,2-dimethyl[1,3]dioxolan-4-yl)methyl]-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-4-ylamine

HRID 598388Notes

Reaction equation

HRID 598388 reaction equation
C1C=C(Cl)C=C(C(OO)=O)C=1.[CH2:12]([O:19][C:20]1[CH:21]=[CH:22][C:23]2[C:24]3[N:32]([CH2:33][CH:34]4[CH2:38][O:37][C:36]([CH3:40])([CH3:39])[O:35]4)[C:31]([CH2:41][O:42][CH2:43][CH3:44])=[N:30][C:25]=3[CH:26]=[N:27][C:28]=2[CH:29]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[NH4+:46].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>ClCCl>[CH2:12]([O:19][C:20]1[CH:21]=[CH:22][C:23]2[C:24]3[N:32]([CH2:33][CH:34]4[CH2:38][O:37][C:36]([CH3:39])([CH3:40])[O:35]4)[C:31]([CH2:41][O:42][CH2:43][CH3:44])=[N:30][C:25]=3[C:26]([NH2:46])=[N:27][C:28]=2[CH:29]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acid2×HCID 670511477-benzyloxy-1-[(2,2-dimethyl[1,3]dioxolan-4-yl)methyl]-2-ethoxymethyl-1H-imidazo[4,5-c]quinoline

Product 1

HCID 575453177-benzyloxy-1-[(2,2-dimethyl[1,3]dioxolan-4-yl)methyl]-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-4-ylamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

3-Chloroperoxybenozic acid (mCPBA) (75% pure, 11.57 g, 50.27 mmol, 1.5 eq) was added to a solution of 7-benzyloxy-1-[(2,2-dimethyl[1,3]dioxolan-4-yl)methyl]-2-ethoxymethyl-1H-imidazo[4,5-c]quinoline (15.00 g, 33.52 mmol. 1 eq) in dichloromethane (200 mL), and the reaction mixture was stirred for two hours. Analysis by thin layer chromatography indicated the reaction was incomplete and additional mCPBA (1.2 g) was added and the reaction was stirred overnight. The reaction mixture was diluted with dichloromethane (300 mL), washed sequentially with 4% aqueous sodium carbonate solution (2×300 mL) and brine (300 mL), and concentrated under reduced pressure to afford a residue. Concentrated ammonium hydroxide (75 mL) was then added to a mixture of the residue in dichloromethane (200 mL) and cooled to 4° C. p-Toluenesulfonyl chloride (2.75 g, 14.44 mmol, 1.1 eq) was added in portions to the reaction mixture and stirred at ambient temperature for 16 hours. The reaction mixture was then diluted with dichloromethane (200 mL), washed with 4M aqueous sodium carbonate solution and separated. The aqueous layer was re-extracted with dichloromethane (200 mL) and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford a brown solid. The crude material was purified by crystallization from diethyl ether to provide 9.8 g of 7-benzyloxy-1-[(2,2-dimethyl[1,3]dioxolan-4yl)methyl]-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-4-ylamine as white plates of solid, mp 186-187° C. 1H-NMR (300 MHz, CDCl3) δ 7.89 (d, J=9.1 Hz, 1H), 7.53-7.29 (m, 6H), 7.05 (dd, J=9.0, 2.6 Hz, 1H), 5.42 (br s, 2H), 5.18 (s, 2H), 4.94 (d, J=12.6 Hz, 1H), 4.83-4.69 (m, 3H), 4.68-4.58 (m, 1H), 4.15 (dd, J=8.6, 6.2 Hz, 1H), 3.86 (dd, J=8.6, 6.1 Hz, 1H), 3.62 (q, J=7.0 Hz, 2H), 1.45 (s, 3H), 1.29 (s, 3H), 1.25 (t, J=7.0 Hz, 3H); 13C-NMR (75 MHz, CDCl3) δ 158.3, 151.7, 149.0, 147.1, 136.8, 134.7, 128.6, 128.0, 127.6, 125.4, 120.9, 113.8, 110.2, 109.7, 108.9, 74.6, 70.0, 66.7, 66.3, 65.3, 48.2, 26.7, 25.1, 15.0; MS (APCI) m/z 463.1 (M+H)+; Anal, calcd for C26H30N4O4: C, 67.51; H, 6.54; N, 12.11. Found: C, 67.29; H, 6.33; N, 12.03.

Workup

  1. stirringthe reaction was stirred overnight
  2. washwashed sequentially with 4% aqueous sodium carbonate solution (2×300 mL) and brine (300 mL)
  3. concentrationconcentrated under reduced pressure
  4. customto afford a residue
  5. additionwas added in portions to the reaction mixture
  6. stirringstirred at ambient temperature for 16 hours
  7. washwashed with 4M aqueous sodium carbonate solution
  8. customseparated
  9. extractionThe aqueous layer was re-extracted with dichloromethane (200 mL)
  10. washthe combined organic layers were washed with brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto afford a brown solid
  15. customThe crude material was purified by crystallization from diethyl ether

Sources & evidence

ORD record
ord-ef99502cf48f472781995d5399c8ec68
Source dataset
uspto-grants-2011_03
Patent number
US07897597B2

Reaction notes

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