Aldoxime → 4-chloro-2-(ethoxymethyl)-1-[2-(3-methyl-1-oxa-2,4-diazaspiro[4,4]non-2-en-4-yl)ethyl]-1H-imidazo[4,5-c]quinoline

HRID 606084Notes

Reaction equation

HRID 606084 reaction equation
[Cl:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:18][O:19][CH2:20][CH3:21])[N:14]([CH2:15][CH2:16][NH2:17])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[C:22]1(=[O:27])[CH2:26][CH2:25][CH2:24][CH2:23]1.S([O-])([O-])(=O)=O.[Mg+2].[CH:34](=[N:36]O)[CH3:35].ClN1C(=O)CCC1=O.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:18][O:19][CH2:20][CH3:21])[N:14]([CH2:15][CH2:16][N:17]3[C:22]4([CH2:26][CH2:25][CH2:24][CH2:23]4)[O:27][N:36]=[C:34]3[CH3:35])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

8

Reactant 6

HCID 7863AldoximeHCID 8452CyclopentanoneHCID 8471TriethylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 31398ChlorosuccinimideHCID 862476222-(4-chloro-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)ethylamine

Product 1

HCID 866168874-chloro-2-(ethoxymethyl)-1-[2-(3-methyl-1-oxa-2,4-diazaspiro[4,4]non-2-en-4-yl)ethyl]-1H-imidazo[4,5-c]quinolineYield 54.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(4-chloro-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)ethylamine (1.00 g, 3.28 mmol), cyclopentanone (0.32 mL, 3.6 mmol), and magnesium sulfate in dichloromethane was stirred at room temperature overnight. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (20 mL) along with N-hydroxyethanimidoyl chloride, which was prepared from acetaldehyde oxime (242 mg, 4.10 mmol) and N-chlorosuccinimide (537 mg, 4.10 mmol) according to the method described in Part G of Example 10. The resulting solution was cooled in an ice bath and triethylamine (0.69 mL, 4.9 mmol) was added. The mixture was allowed to warm slowly to room temperature and stirred overnight. The work-up and purification procedures described in Part G of Example 10 were followed to provide 770 mg of 4-chloro-2-(ethoxymethyl)-1-[2-(3-methyl-1-oxa-2,4-diazaspiro[4,4]non-2-en-4-yl)ethyl]-1H-imidazo[4,5-c]quinoline as a clear, colorless oil.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane (20 mL) along with N-hydroxyethanimidoyl chloride, which
  4. temperatureThe resulting solution was cooled in an ice bath
  5. temperatureto warm slowly to room temperature
  6. stirringstirred overnight
  7. customThe work-up and purification procedures

Sources & evidence

ORD record
ord-70ff8d3d1cae4c6dbf645630c8096baa
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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