Potassium Iodide → 4-[2-((R)-1-Phenyl-ethylamino)-quinoxalin-6-yl]-pyrazole-1-carboxylic acid tert-butyl ester

HRID 1020744Notes

Reaction equation

HRID 1020744 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][C@@H:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:14])[CH:6]=[N:5]2.[C:21]([N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>O1CCOCC1.C(OCC)(=O)C>[C:24]([O:23][C:21]([N:28]1[CH:32]=[C:31]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([NH:12][C@@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[CH:6]=[N:5]3)[CH:30]=[N:29]1)=[O:22])([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 66797257(6-Bromo-quinoxalin-2-yl)-((R)-1-phenyl-ethyl)-amine

Product 1

HCID 667975654-[2-((R)-1-Phenyl-ethylamino)-quinoxalin-6-yl]-pyrazole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
108 °C

Procedure

A mixture of (6-Bromo-quinoxalin-2-yl)-((R)-1-phenyl-ethyl)-amine (0.42 g, 1 eq, 1.28 mmol), 1-boc-4-pyrazole boronic acid pinacol ester (0.45 g, 1.2 eq, 1.53 mmol), caesium carbonate (1.66 g, 4.0 eq, 5.1 mmol) and potassium iodide (0.021 g, 0.1 eq, 0.13 mmol) in 1,4-dioxane (20 mL) was degassed at RT under vacuum and then placed under an atmosphere of nitrogen. The process was repeated twice and Fu's catalyst (Bis(tri-tert-butylphosphine)palladium(0)) (0.033 g, 0.05 eq, 0.06 mmol) was added at room temperature. The reaction mixture was heated at 108° C. in a microwave reactor for 180 minutes. After completion of the reaction (confirmed by TLC), the reaction mixture was diluted with ethyl acetate (200 mL) and then washed with water (50 mL×3) and brine (50 mL). The organic layer was dried and concentrated to give the crude product.

Workup

  1. customwas degassed at RT under vacuum
  2. additionFu's catalyst (Bis(tri-tert-butylphosphine)palladium(0)) (0.033 g, 0.05 eq, 0.06 mmol) was added at room temperature
  3. customAfter completion of the reaction (confirmed by TLC)
  4. washwashed with water (50 mL×3) and brine (50 mL)
  5. customThe organic layer was dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-928e58d805414bc5adcbbf91df20943a
Source dataset
uspto-grants-2014_05
Patent number
US08716473B2

Reaction notes

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