Potassium Iodide → 4-{2-[(4-Fluoro-3-trifluoromethyl-benzyl)-methyl-amino]-quinoxalin-6-yl}-pyrazole-1-carboxylic acid tert-butyl ester

HRID 1020741Notes

Reaction equation

HRID 1020741 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:12]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([C:22]([F:25])([F:24])[F:23])[CH:16]=1)[CH3:13])[CH:6]=[N:5]2.[C:26]([N:33]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[N:34]1)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>O1CCOCC1.C(OCC)(=O)C>[C:29]([O:28][C:26]([N:33]1[CH:37]=[C:36]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([N:12]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[C:17]([C:22]([F:24])([F:23])[F:25])[CH:16]=2)[CH3:13])[CH:6]=[N:5]3)[CH:35]=[N:34]1)=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 66797280(6-Bromo-quinoxalin-2-yl)-(4-fluoro-3-trifluoromethyl-benzyl)-methyl-amine

Product 1

HCID 667976124-{2-[(4-Fluoro-3-trifluoromethyl-benzyl)-methyl-amino]-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)-(4-fluoro-3-trifluoromethyl-benzyl)-methyl-amine (0.35 g, 1 eq, 0.84 mmol), 1-Boc-4-pyrazole boronic acid pinacol ester (0.3 g, 1.2 eq, 1.01 mmol), caesium carbonate (1.1 g, 4.0 eq, 3.3 mmol) and potassium iodide (0.014 g, 0.1 eq, 0.84 mmol) in 1,4-dioxane (15 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)) (0.02 g, 0.05 eq, 0.04 mmol) was added at room temperature. The reaction mixture was heated at 108° C. in a microwave reactor for 180 min. After completion of the reaction (confirmed by TLC), the organic mixture was diluted with ethyl acetate (325 mL) and washed with water (100 mL×3) followed by brine (100 mL). The organic solvent was dried and concentrated to give a solid residue.

Workup

  1. customwas degassed at RT under vacuum
  2. additionFu's catalyst (Bis(tri-tert-butylphosphine)palladium(0)) (0.02 g, 0.05 eq, 0.04 mmol) was added at room temperature
  3. customAfter completion of the reaction (confirmed by TLC)
  4. washwashed with water (100 mL×3)
  5. customThe organic solvent was dried
  6. concentrationconcentrated
  7. customto give a solid residue

Sources & evidence

ORD record
ord-e98124baa28745baa727ff14bbcee1ab
Source dataset
uspto-grants-2014_05
Patent number
US08716473B2

Reaction notes

Loading…