Triethylamine → 4-chloro-2-(ethoxymethyl)-1-[(3-phenylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline

HRID 606042Notes

Reaction equation

HRID 606042 reaction equation
[OH:1][N:2]=[C:3](Cl)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:11][C:12]1[C:21]2[N:22]=[C:23]([CH2:28][O:29][CH2:30][CH3:31])[N:24]([CH2:25][C:26]#[CH:27])[C:20]=2[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:13]=1.C(N(CC)CC)C>ClCCl>[Cl:11][C:12]1[C:21]2[N:22]=[C:23]([CH2:28][O:29][CH2:30][CH3:31])[N:24]([CH2:25][C:26]3[O:1][N:2]=[C:3]([C:4]4[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=4)[CH:27]=3)[C:20]=2[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:13]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2756315N-hydroxybenzenecarboximidoyl chloride2×HCID 862475854-chloro-2-(ethoxymethyl)-1-prop-2-ynyl-1H-imidazo[4,5-c]quinoline

Product 1

HCID 866168724-chloro-2-(ethoxymethyl)-1-[(3-phenylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-Hydroxybenzenecarboximidoyl chloride (prepared as described in Part A of Example 2, 1.72 g, 10.5 mmol) was added to a solution of 4-chloro-2-(ethoxymethyl)-1-prop-2-ynyl-1H-imidazo[4,5-c]quinoline (3.00 g, 10.0 mmol) and triethylamine (1.70 mL, 12.0 mmol) in dichloromethane (40 mL). The solution was heated at reflux under a nitrogen atmosphere for 3.5 hours and additional N-hydroxybenzenecarboximidoyl chloride (0.1 g) was added. The solution was heated at reflux for one hour more, then was allowed to cool to room temperature and was diluted with dichloromethane. The solution was transferred to a separatory funnel and was washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography (silica gel, gradient elution from 4:1 to 3:2 hexanes/ethyl acetate) to provide pure 4-chloro-2-(ethoxymethyl)-1-[(3-phenylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline (1.48 g).

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux under a nitrogen atmosphere for 3.5 hours
  3. temperatureThe solution was heated
  4. temperatureat reflux for one hour more
  5. customThe solution was transferred to a separatory funnel
  6. washwas washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by flash chromatography (silica gel, gradient elution from 4:1 to 3:2 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-17e905e7bcf543f28b6b5973b4656662
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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