3-Pyridine aldoxime → 4-chloro-2-(ethoxymethyl)-1-[(3-pyridin-3-ylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline

HRID 606047Notes

Reaction equation

HRID 606047 reaction equation
ClN1C(=O)CCC1=O.[N:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]=[N:16][OH:17])[CH:10]=1.[Cl:18][C:19]1[C:28]2[N:29]=[C:30]([CH2:35][O:36][CH2:37][CH3:38])[N:31]([CH2:32][C:33]#[CH:34])[C:27]=2[C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[N:20]=1.C(N(CC)CC)C>O1CCCC1>[Cl:18][C:19]1[C:28]2[N:29]=[C:30]([CH2:35][O:36][CH2:37][CH3:38])[N:31]([CH2:32][C:33]3[O:17][N:16]=[C:15]([C:11]4[CH:10]=[N:9][CH:14]=[CH:13][CH:12]=4)[CH:34]=3)[C:27]=2[C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[N:20]=1

Participants

6

Reactant 4

HCID 6943-Pyridine aldoximeHCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 862475854-chloro-2-(ethoxymethyl)-1-prop-2-ynyl-1H-imidazo[4,5-c]quinoline

Product 1

HCID 866168744-chloro-2-(ethoxymethyl)-1-[(3-pyridin-3-ylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinolineYield 55.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

N-Chlorosuccinimide (1.09 g, 8.19 mmol) was added to a 6° C. solution of 3-pyridinecarboxaldehyde oxime (1.00 g, 8.19 mmol) in tetrahydrofuran (THF) (25 mL). The solution was heated at 50° C. for 2 h. 4-Chloro-2-(ethoxymethyl)-1-prop-2-ynyl-1H-imidazo[4,5-c]quinoline (prepared as described in Part D of Example 3, 1.96 g, 6.55 mmol) and triethylamine (1.70 mL, 12.3 mmol) were added to the reaction, which was heated at 50° C. for 17 hours. The volatiles were removed under reduced pressure and the residue was partitioned between dichloromethane and saturated aqueous potassium carbonate. The aqueous layer was extracted multiple times with dichloromethane and chloroform. The organic layers were combined, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography (silica gel, gradient elution with 1:1 to 1:4 hexanes/ethyl acetate) to yield 4-chloro-2-(ethoxymethyl)-1-[(3-pyridin-3-ylisoxazol-5-yl)methyl]-1H-imidazo[4,5-c]quinoline (1.52 g).

Workup

  1. temperaturewas heated at 50° C. for 17 hours
  2. customThe volatiles were removed under reduced pressure
  3. customthe residue was partitioned between dichloromethane and saturated aqueous potassium carbonate
  4. extractionThe aqueous layer was extracted multiple times with dichloromethane and chloroform
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (silica gel, gradient elution with 1:1 to 1:4 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-d03a359966df4dc5ab0c521c908b3f26
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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