Trimethyl orthoacetate → 2-methyl-1-{2-[2-(methylsulfonyl)ethoxy]ethyl}-1H-imidazo[4,5-c]quinoline

HRID 547289Notes

Reaction equation

HRID 547289 reaction equation
[C:1](OC)(OC)(OC)[CH3:2].[CH3:9][S:10]([CH2:13][CH2:14][O:15][CH2:16][CH2:17][NH:18][C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[CH:21][C:20]=1[NH2:29])(=[O:12])=[O:11].Cl.N1C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[N:18]([CH2:17][CH2:16][O:15][CH2:14][CH2:13][S:10]([CH3:9])(=[O:12])=[O:11])[C:19]2[C:28]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[N:22]=[CH:21][C:20]=2[N:29]=1

Participants

5

Reactant 3

HCID 15050Trimethyl orthoacetateHCID 10176127Pyridinium chlorideHCID 86064731N4-{2-[2-(methylsulfonyl)ethoxy]ethyl}quinoline-3,4-diamine

Product 1

HCID 672036272-methyl-1-{2-[2-(methylsulfonyl)ethoxy]ethyl}-1H-imidazo[4,5-c]quinolineYield 70.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Trimethyl orthoacetate (1 g, 8.1 mmol) was added to a mixture of N4-{2-[2-(methylsulfonyl)ethoxy]ethyl}quinoline-3,4-diamine (˜2.3 g, ˜7.4 mmol) and toluene (45 mL). Pyridine hydrochloride (0.25 g) was added and the reaction mixture was heated to reflux with the volatiles being collected in a Dean Stark trap. Pyridine was added to help solubilize the starting material. After 2 hours the reaction mixture was concentrated under reduced pressure to provide a dark oil. This material was purified by column chromatography (silica gel eluting sequentially with 95/5 dichloromethane/methanol and 9/1 dichloromethane/methanol) to provide 1.75 g of 2-methyl-1-{2-[2-(methylsulfonyl)ethoxy]ethyl}-1H-imidazo[4,5-c]quinoline as a white foam.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux with the volatiles
  3. custombeing collected in a Dean Stark trap
  4. additionPyridine was added
  5. concentrationAfter 2 hours the reaction mixture was concentrated under reduced pressure
  6. customto provide a dark oil
  7. customThis material was purified by column chromatography (silica gel eluting sequentially with 95/5 dichloromethane/methanol and 9/1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-ab312a549df742d68898c12bd5443951
Source dataset
uspto-grants-2011_05
Patent number
US07939526B2

Reaction notes

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