Water → tert-butyl 4-({[2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-yl]oxy}acetyl)piperazine-1-carboxylate

HRID 2203583Notes

Reaction equation

HRID 2203583 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:19][CH2:20][CH3:21])[C:7]2[C:16]3[CH:15]=[C:14]([OH:17])[CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:18]=1)[CH3:2].Br[CH2:23][C:24]([N:26]1[CH2:31][CH2:30][N:29](NC(OC(C)(C)C)=O)[CH2:28][CH2:27]1)=[O:25].[C:40](=[O:43])([O-])[O-:41].[K+].[K+].O>CN(C=O)C>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:19][CH2:20][CH3:21])[C:7]2[C:16]3[CH:15]=[C:14]([O:17][CH2:23][C:24]([N:26]4[CH2:27][CH2:28][N:29]([C:40]([O:41][C:16]([CH3:7])([CH3:15])[CH3:11])=[O:43])[CH2:30][CH2:31]4)=[O:25])[CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:18]=1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 670510882-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol2×HCID 68899328Tert-butyl 4-(2-bromoacetyl)piperazine-1-carbamate

Product 1

HCID 68975457tert-butyl 4-({[2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-yl]oxy}acetyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

The synthesis of 2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol is described in Parts A-I of Example 2. A mixture of 2-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol (4.5 g, 15.8 mmol), tert-butyl 4-(2-bromoacetyl)piperazine-1-carbamate (4.57 g, 14.9 mmol), and potassium carbonate (3.27 g, 23.7 mmol) in DMF (158 mL) was heated to 55° C. for 2.5 hours, then was allowed to cool to room temperature and was stirred for 16 hours. The solution was poured into water (500 mL), which was extracted with diethyl ether (300 mL), ethyl acetate (300 mL) and dichloromethane (300 mL). The combined organic layers were concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, gradient elution with 0-5% methanol in dichloromethane to provide 7.9 g of tert-butyl 4-({[2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-yl]oxy}acetyl)piperazine-1-carboxylate as a tan waxy solid that contained 15% of DMF by weight.

Workup

  1. temperatureto cool to room temperature
  2. extractionwas extracted with diethyl ether (300 mL), ethyl acetate (300 mL) and dichloromethane (300 mL)
  3. concentrationThe combined organic layers were concentrated under reduced pressure
  4. customThe crude product was purified by flash chromatography (
  5. washsilica gel, gradient elution with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-75c10c20183948899b8c8529d3f2bba2
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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