2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → HCID 67193678, compound

HRID 1853296Notes

Reaction equation

HRID 1853296 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[NH:10][CH2:9][C:8]2[N:11]=[CH:12][N:13]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:7]=2[CH2:6]1)=[O:4].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[N:10]=[CH:9][C:8]2[N:11]=[CH:12][N:13]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:7]=2[CH:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 14457551HCID 14457551, compound

Product 1

HCID 67193678HCID 67193678, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of H-His-(Bzl)-OH (2.0 g, 8.16 mmol) and formaldehyde (37% in water, 0.92 ml, 12.24 mmol) in water (16 ml) was heated to reflux for 4 hours and concentrated to dryness. The residue was dissolved in methanol (4.6 ml) cooled to 0° C. and treated with thionyl chloride (0.6 ml, 8.12 mmol). The reaction mixture was reflux for 2.5 hours and concentrated. The solid was dissolved in dichloromethane, washed with a saturated solution of sodium hydrogenocarbonate, brine, dried over sodium sulfate and concentrated to dryness to yield 1-Benzyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester (1.58 g, 71%). The ester was dissolved in tetrahydrofuran (26 ml), cooled to 0° C. and treated with 2,3-Dichloro-5,6-dicyanobenzoquinone (2.9 g, 12.81 mmol) in tetrahydrofuran (26 ml) and the reaction mixture was reflux for 4 hours. The solvent was removed and the black residue was dissolved in dichloromethane and treated with a 1M aqueous solution of sodium hydroxide. The aqueous solution was extracted several times with dichloromethane. The combined organic extracts were washed with brine, dried over sodium sulfate, concentrated and purified by flash chromatography over silica gel (gradient ethyl acetate/methanol: 0-10%) to yield 1-Benzyl-1H-imidazo[4,5-c]pyridin-6-carboxylic acid methyl ester (525 mg, 34%) as a beige solid.

Workup

  1. temperaturethe reaction mixture was reflux for 4 hours
  2. customThe solvent was removed
  3. dissolutionthe black residue was dissolved in dichloromethane
  4. additiontreated with a 1M aqueous solution of sodium hydroxide
  5. extractionThe aqueous solution was extracted several times with dichloromethane
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. custompurified by flash chromatography over silica gel (gradient ethyl acetate/methanol: 0-10%)

Sources & evidence

ORD record
ord-fd5f2d7d209b4fecaf8ba904d06a55f1
Source dataset
uspto-grants-2015_02
Patent number
US08962627B2

Reaction notes

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