Ethyl 2-chloroethanecarboximidate hydrochloride → 1-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline

HRID 549112

Reaction equation

HRID 549112 reaction equation
[Si:1]([O:8][C:9]([CH3:33])([CH3:32])[C@H:10]([NH:20][C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=[CH:23][C:22]=1[NH2:31])[CH2:11][O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.[Cl:35][CH2:36][C:37](=N)OCC>ClCCCl>[Si:1]([O:8][C:9]([CH3:33])([CH3:32])[C@H:10]([N:20]1[C:21]2[C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N:24]=[CH:23][C:22]=2[N:31]=[C:37]1[CH2:36][Cl:35])[CH2:11][O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 12470659Ethyl 2-chloroethanecarboximidate hydrochloride2×HCID 86624120HCID 86624120, compound

Product 1

HCID 671569791-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinolineYield 25.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

N4-[(1R)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]quinoline-3,4-diamine (6.12 g, 12.5 mmol) was dissolved in 100 mL of dry 1,2-dichloroethane and the solution was stirred under N2. Ethyl 2-chloroethanimidoate hydrochloride (2.77 g, 17.5 mmol) was then added and the reaction mixture was heated to 70° C. After stirring for 3 days, the reaction mixture was treated with an additional 1.00 g of ethyl 2-chloroethanimidoate hydrochloride and the reaction temperature was increased to 85° C. After stirring for 2 days, the reaction was cooled and the 1,2-dichloroethane was removed under reduced pressure. The resulting material was partitioned between 200 mL of saturated NaHCO3 solution and 200 mL of ethyl acetate. The layers were separated and the organic portion was washed with H2O and brine. The organic portion was then dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (SiO2, 25%-50% ethyl acetate/hexanes) gave 1-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline (1.74 g) as a golden syrup.

Workup

  1. stirringAfter stirring for 3 days
  2. temperaturethe reaction temperature was increased to 85° C
  3. stirringAfter stirring for 2 days
  4. temperaturethe reaction was cooled
  5. customthe 1,2-dichloroethane was removed under reduced pressure
  6. customThe resulting material was partitioned between 200 mL of saturated NaHCO3 solution and 200 mL of ethyl acetate
  7. customThe layers were separated
  8. washthe organic portion was washed with H2O and brine
  9. dry with materialThe organic portion was then dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c44087bbcad04a0ebdf88c4929188f65
Source dataset
uspto-grants-2011_05
Patent number
US07943609B2

Linked notes

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