Imidazole → HCID 58358522, compound

HRID 218033Notes

Reaction equation

HRID 218033 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([NH:9][C:10]12[CH2:19][CH:14]3[CH2:15][CH:16]([CH2:18][C:12]([NH:20][C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25](Cl)[N:24]=4)=[O:22])([CH2:13]3)[CH2:11]1)[CH2:17]2)=[O:8].[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu+2].CC(N(C)C)=O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([NH:9][C:10]12[CH2:19][CH:14]3[CH2:15][CH:16]([CH2:18][C:12]([NH:20][C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([N:30]5[CH:34]=[CH:33][N:32]=[CH:31]5)[N:24]=4)=[O:22])([CH2:13]3)[CH2:11]1)[CH2:17]2)=[O:8]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 10796Cesium carbonateHCID 59161108HCID 59161108, compound2×

Product 1

HCID 58358522HCID 58358522, compoundYield 20.3%

Reagents, catalysts & solvents 2

HCID 27099Cupric cationCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
180 °C

Procedure

To a microwave vial was added a stir bar, 6-chloro-pyridine-2-carboxylic acid {3-[(pyridine-2-carbonyl)-amino]-adamantan-1-yl}-amide (Intermediate 4, 20 mg, 0.05 mmol), copper (II) acetoacetonate (20 mg), DMA (1 mL), imidazole (50 mg, 0.73 mmol) and cesium carbonate (60 mg, 0.15 mmol). The mixture was heated at 180° C. under microwave irradiation for 15 minutes. Solvent was removed in a high performance solvent evaporation system HT-4X (Genevac, Inc., supra). The residue was dissolved in DCM (2 mL), washed with aq. 1 N NaOH (2 mL), and water (2×2 mL). After removing the solvent, the residue was purified on a RP-HPLC/MS system (Gradient: acetonitrile in water with a cycle time of 5 min. Flow rate: 100 mL/min. Mobile phase additive: 25 mM of ammonium acetate. Column: Inertsil® C8, 30×50 mm, 5 μm particle size (GL Sciences, Tokyo, Japan) to afford 4.5 mg of the title compound, 6-imidazol-1-yl-pyridine-2-carboxylic acid {3-[(pyridine-2-carbonyl)-amino]-adamantan-1-yl}-amide. ESI-MS m/z: 443.5 (M+H)+.

Workup

  1. additionTo a microwave vial was added a stir bar
  2. customSolvent was removed in a high performance solvent evaporation system HT-4X (Genevac, Inc., supra)
  3. dissolutionThe residue was dissolved in DCM (2 mL)
  4. washwashed with aq. 1 N NaOH (2 mL), and water (2×2 mL)
  5. customAfter removing the solvent
  6. customthe residue was purified on a RP-HPLC/MS system (Gradient
  7. customwith a cycle time of 5 min

Sources & evidence

ORD record
ord-8b1464f0f54b4af080c2898787193528
Source dataset
uspto-grants-2012_06
Patent number
US08198275B2

Reaction notes

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