Potassium Carbonate → 2-(4,5-Difluoro-2-phenylamino-phenylamino)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

HRID 343157Notes

Reaction equation

HRID 343157 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:16])[C:5]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][C:7]=1[F:8].C(=O)([O-])[O-].[K+].[K+].Br[CH2:24][C:25]([N:27]([CH:36]([CH3:38])[CH3:37])[C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)=[O:26]>CN(C)C=O>[F:8][C:7]1[C:2]([F:1])=[CH:3][C:4]([NH:16][CH2:24][C:25]([N:27]([CH:36]([CH3:38])[CH3:37])[C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)=[O:26])=[C:5]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 107795342-Bromo-N-isopropyl-N-(4-methoxyphenyl)acetamide2×HCID 543941314,5-difluoro-N-phenyl-benzene-1,2-diamine

Product 1

HCID 539192522-(4,5-Difluoro-2-phenylamino-phenylamino)-N-isopropyl-N-(4-methoxy-phenyl)-acetamideYield 96.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3.004 g of 4,5-difluoro-N-phenyl-benzene-1,2-diamine (J. Gen. Chem. USSR (Engl. Transl.), 1964, 34), 1.910 g of potassium carbonate (13.82 mmol, 1.0 equiv), and 3.956 g of 2-bromo-N-isopropyl-N-(4-methoxy-phenyl)-acetamide (13.82 mmol, 1.0 equiv) in 20 mL of dimethylformamide is stirred under nitrogen at ambient temperature for 16 h. An additional 3.00 g of 2-bromo-N-isopropyl-N-(4-methoxy-phenyl)-acetamide (10.5 mmol, 0.75 equiv) is added and the reaction is heated at 50° C. for 2 h. The mixture is cooled to ambient temperature and then partitioned between diethyl ether and 1:1 water/saturated aqueous brine. The layers were separated and the aqueous layer is back-extracted twice with diethyl ether. The ether layers were combined, washed with saturated aqueous brine, dried over anhydrous sodium sulfate and then evaporated in vacuo to a residue. The residue is purified on flash grade silica gel using 10-20% ethyl acetate in hexane. The appropriate fractions were combined, evaporated in vacuo and dried under vacuum to provide 5.62 g of 2-(4,5-Difluoro-2-phenylamino-phenylamino)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide as a solid: Low resolution MS (FAB)m/e 425 (M+); TLC Rf =0.43 (ethyl acetate/hexane 3:7).

Workup

  1. temperaturethe reaction is heated at 50° C. for 2 h
  2. temperatureThe mixture is cooled to ambient temperature
  3. custompartitioned between diethyl ether and 1:1 water/saturated aqueous brine
  4. customThe layers were separated
  5. extractionthe aqueous layer is back-extracted twice with diethyl ether
  6. washwashed with saturated aqueous brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customevaporated in vacuo to a residue
  9. customThe residue is purified on flash grade silica gel using 10-20% ethyl acetate in hexane
  10. customevaporated in vacuo
  11. customdried under vacuum

Sources & evidence

ORD record
ord-46408acfb93643c1ade1371630567b88
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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