Potassium Carbonate → {6-Methoxy-5-[2-methoxy-4-(trifluoromethoxy)phenyl]pyrazin-2-yl}[(4-methoxyphenyl)methyl]amine

HRID 349181Notes

Reaction equation

HRID 349181 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[C:8]1[N:9]=[CH:10][C:11]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[N:12][C:13]=1[O:14][CH3:15].[CH3:26][O:27][C:28]1[CH:33]=[C:32]([O:34][C:35]([F:38])([F:37])[F:36])[CH:31]=[CH:30][C:29]=1B(O)O>C1(C)C=CC=CC=1.[OH-].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:15][O:14][C:13]1[N:12]=[C:11]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[CH:10]=[N:9][C:8]=1[C:29]1[CH:30]=[CH:31][C:32]([O:34][C:35]([F:37])([F:38])[F:36])=[CH:33][C:28]=1[O:27][CH3:26]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 22490042(2-Methoxy-4-(trifluoromethoxy)phenyl)boronic acidHCID 23595037(5-Bromo-6-methoxypyrazin-2-yl)[(4-methoxyphenyl)methyl]amine

Product 1

HCID 22249073{6-Methoxy-5-[2-methoxy-4-(trifluoromethoxy)phenyl]pyrazin-2-yl}[(4-methoxyphenyl)methyl]amineYield 88.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 14798Sodium HydroxideSolvent

Procedure

Tetrakis(triphenylphosphine)palladium(0) (100 mg) and potassium carbonate (2.0 M, 2.0 mL) are added to a stirred solution of (5-bromo-6-methoxypyrazin-2-yl)[(4-methoxyphenyl)methyl]amine (0.80 g, 2.50 mmol) and 2-methoxy-4-trifluoromethoxy benzeneboronic acid (1.75 g, 7.5 mmol) in toluene (25 mL). The mixture is heated to 85 C for 8 hours, cooled to room temperature, diluted with 2.0 M sodium hydroxide and extracted twice with 1:1 hexane-ethyl ether. The combined extracts are dried (sodium sulfate), filtered and concentrated. The residue is purified by flash chromatography, eluting with 60% hexanes in ether to give {6-methoxy-5-[2-methoxy-4-(trifluoromethoxy)phenyl]pyrazin-2yl}[(4-methoxyphenyl)methyl]amine (967 mg).

Workup

  1. temperatureThe mixture is heated to 85 C for 8 hours
  2. extractionextracted twice with 1:1 hexane-ethyl ether
  3. dry with materialThe combined extracts are dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by flash chromatography
  7. washeluting with 60% hexanes in ether

Sources & evidence

ORD record
ord-7a61a56c157344a2bcfaa2b196cbff3f
Source dataset
uspto-grants-2007_02
Patent number
US07179807B2

Reaction notes

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