4-Toluenesulfonyl chloride → 7-benzyloxy-2-ethoxymethyl-N-isopropyl-1H-imidazo[4,5-c]quinoline-1,4-diamine

HRID 1373962Notes

Reaction equation

HRID 1373962 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13]3[N:21]([NH:22][CH:23]([CH3:25])[CH3:24])[C:20]([CH2:26][O:27][CH2:28][CH3:29])=[N:19][C:14]=3[CH:15]=[N:16][C:17]=2[CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[NH4+:31].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl.O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13]3[N:21]([NH:22][CH:23]([CH3:25])[CH3:24])[C:20]([CH2:26][O:27][CH2:28][CH3:29])=[N:19][C:14]=3[C:15]([NH2:31])=[N:16][C:17]=2[CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 21075797N-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)isopropylamine

Product 1

HCID 100926957-benzyloxy-2-ethoxymethyl-N-isopropyl-1H-imidazo[4,5-c]quinoline-1,4-diamine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

A solution of N-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)isopropylamine (6.63 g, 17.0 mmol) in 90 mL of CHCl3 was treated with MPCBA (6.29 g, 25.5 mmol, 70%). After 3 h, HPLC and LC/MS indicated complete conversion to the intermediate 5-N-oxide. The reaction mixture was then treated with concentrated ammonium hydroxide solution (30 mL, 30%). The biphasic reaction mixture was stirred vigorously while p-toluenesulfonyl chloride (3.40 g, 17.9 mmol) was added. After 45 min, LC/MS indicated complete conversion to the 4-amine. The reaction mixture was diluted with 30 mL of water and 45 mL of CHCl3 and separated. The organic portion was washed with 10% Na2CO3 solution (50 mL) and water (50 mL). The combined aqueous portions were then back-extracted with CHCl3 (25 mL). The combined organic portions were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated to yield a tan solid. The solid was purified by chromatography (SiO2, 96:4 CHCl3:MeOH) to give 5.90 g of 7-benzyloxy-2-ethoxymethyl-N1-isopropyl-1H-imidazo[4,5-c]quinoline-1,4-diamine as a light tan solid.

Workup

  1. customThe biphasic reaction mixture
  2. additionwas added
  3. waitAfter 45 min
  4. customseparated
  5. washThe organic portion was washed with 10% Na2CO3 solution (50 mL) and water (50 mL)
  6. extractionThe combined aqueous portions were then back-extracted with CHCl3 (25 mL)
  7. washThe combined organic portions were washed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto yield a tan solid
  12. customThe solid was purified by chromatography (SiO2, 96:4 CHCl3:MeOH)

Sources & evidence

ORD record
ord-62df492daae64025814b94e1943b0625
Source dataset
uspto-grants-2007_01
Patent number
US07163947B2

Reaction notes

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