Diisopropylethylamine → N-(3-bromo-2-methylphenyl)-1H-imidazole-2-carboxamide

HRID 1811017Notes

Reaction equation

HRID 1811017 reaction equation
[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[NH:10]1[CH:14]=[CH:13][N:12]=[C:11]1[C:15](O)=[O:16].C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)CCl.C(Cl)Cl.C1COCC1>[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([NH:5][C:15]([C:11]2[NH:10][CH:14]=[CH:13][N:12]=2)=[O:16])[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 1235383-Bromo-o-toluidineHCID 181649HOAt2×HCID 5743211H-Imidazole-2-carboxylic acid2×

Product 1

HCID 66606432N-(3-bromo-2-methylphenyl)-1H-imidazole-2-carboxamide

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

Step 1 A solution of 3-bromo-2-methylaniline (0.63 g, 3.39 mmol), 1H-imidazole-2-carboxylic acid (0.455 g, 4.06 mmol), HOAT (0.830 g, 6.10 mmol), and EDC (1.298 g, 6.77 mmol) in 2:1 DCM-THF (100 mL) was treated with DIEA (1.774 mL, 10.16 mmol) and stirred at rt overnight. Additional 1H-imidazole-2-carboxylic acid (0.6 eq, 0.228 g), EDC (0.64 g), HOAT (0.41 g), and DIEA (0.8 mL) were added and the mixture was stirred at rt for 6 days. The mixture was partitioned between NaHCO3 (aq) and DCM, and the organic phase was washed with brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from DCM to 94:6 DCM-methanol) to provide N-(3-bromo-2-methylphenyl)-1H-imidazole-2-carboxamide as a solid (80% purity, 0.76 g, 64%). Mass spectrum m/z 280, 282 (M+H)+.

Workup

  1. stirringthe mixture was stirred at rt for 6 days
  2. customThe mixture was partitioned between NaHCO3 (aq) and DCM
  3. washthe organic phase was washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (
  7. washeluting with a gradient from DCM to 94:6 DCM-methanol)

Sources & evidence

ORD record
ord-a6e3ae5dd0264e00ba6332cfb14d2257
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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