Phosphorus trichloride → 7-bromo-2-ethoxymethyl-1-(2-piperazin-1-ylethyl)-1H-imidazo[4,5-c]quinolin-4-amine dihydrochloride

HRID 9445

Reaction equation

HRID 9445 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:31][O:32][CH2:33][CH3:34])[N:14]([CH2:15][CH2:16][N+:17]3([O-])[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([Br:35])=[CH:5][C:4]=2[N:3]=1.P(Cl)(Cl)[Cl:37]>C(Cl)(Cl)Cl.O>[ClH:37].[ClH:37].[Br:35][C:6]1[CH:7]=[CH:8][C:9]2[C:10]3[N:14]([CH2:15][CH2:16][N:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[C:13]([CH2:31][O:32][CH2:33][CH3:34])=[N:12][C:11]=3[C:2]([NH2:1])=[N:3][C:4]=2[CH:5]=1

Participants

5

Reactant 2

HCID 24387Phosphorus trichlorideHCID 21984440tert-butyl 4-[2-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-4-oxidopiperazine-1-carboxylate

Product 1

HCID 219841297-bromo-2-ethoxymethyl-1-(2-piperazin-1-ylethyl)-1H-imidazo[4,5-c]quinolin-4-amine dihydrochlorideYield 84.2%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
4 °C

Procedure

A solution of tert-butyl 4-[2-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-4-oxidopiperazine-1-carboxylate (8.84 g, 16.1 mmol) in chloroform (400 mL) was cooled to 4° C. Phosphorous trichloride (9.82 mL, 113 mmol) was added dropwise, and the reaction was stirred for 45 minutes at 4° C. Water (one drop) was added to the reaction, which was allowed to warm to ambient temperature. The chloroform was removed under reduced pressure, and the residue was dissolved in ethanol (150 mL). Hydrogen chloride (21.5 mL of a 3 M solution in ethanol) was added, and the reaction was heated at reflux for 25 minutes. The reaction was allowed to cool to room temperature; a precipitate formed and was isolated by filtration to provide 6.86 g of 7-bromo-2-ethoxymethyl-1-(2-piperazin-1-ylethyl)-1H-imidazo[4,5-c]quinolin-4-amine dihydrochloride as a light yellow solid.

Workup

  1. temperatureto warm to ambient temperature
  2. customThe chloroform was removed under reduced pressure
  3. dissolutionthe residue was dissolved in ethanol (150 mL)
  4. additionHydrogen chloride (21.5 mL of a 3 M solution in ethanol) was added
  5. temperaturethe reaction was heated
  6. temperatureat reflux for 25 minutes
  7. temperatureto cool to room temperature
  8. customa precipitate formed
  9. customwas isolated by filtration

Sources & evidence

ORD record
ord-fde1062fb7e5468ca3c9b1d8f714ccd0
Source dataset
uspto-grants-2006_08
Patent number
US07091214B2

Linked notes

Loading…