Acrylamide → US9321721, Example 6

HRID 631776Notes

Reaction equation

HRID 631776 reaction equation
[C:1]([NH2:5])(=[O:4])[CH:2]=[CH2:3].[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[NH:17][C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=1)=[O:19]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[NH:17][C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24](/[CH:3]=[CH:2]/[C:1]([NH2:5])=[O:4])=[CH:23][CH:22]=1)=[O:19]

Participants

4

Reactant 2

HCID 6579AcrylamideHCID 690085641-[2-Fluoro-5-(trifluoromethyl)phenyl]-3-(4-iodophenyl)urea

Product 1

HCID 90386808US9321721, Example 6Yield 49%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst2×

Procedure

A mixture of acrylamide (6.2 mg, 0.087 mmol), 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-(4-iodophenyl)urea (9.2 mg, 0.022 mmol), and palladium(II) acetate (1.9 mg, 0.0087 mmol) in 0.6 mL degassed DMF:triethylamine (1:1) was reacted at 90° C. After 2.5 hours, the heating was stopped and the reaction stored at rt for 3 days in the dark. Then a catalytic amount of palladium(II) acetate was added and the heating resumed at 90° C. for 7.5 hours, then the temperature lowered to 65° C. for 16 hours. The reaction was partitioned between EtOAc and H2O/brine mixture. The EtOAc layer was washed with dilute aqueous HCl, then aqueous NaHCO3, brine, dried with anhydrous Na2SO4 and evaporated. The resulting solid was chromatographed eluting with CHCl3/MeOH and then triturated with a CHCl3 plus 40% EtOAc/hexane mixture to give the title compound as a light tan solid (3.9 mg, 49%). 1H NMR (Acetone-d6) δ: 8.76-8.83 (m, 2H), 8.40 (d, J=2.6 Hz, 1H), 7.58-7.63 (m, 2H), 7.37-7.57 (m, 5H), 6.91 (br. s, 1H), 6.63 (d, J=15.8 Hz, 1H), 6.32 (br. s, 1H)

Workup

  1. customdegassed DMF:triethylamine (1:1)
  2. customwas reacted at 90° C
  3. waitthe reaction stored at rt for 3 days in the dark
  4. waitthe heating resumed at 90° C. for 7.5 hours
  5. waitthe temperature lowered to 65° C. for 16 hours
  6. customThe reaction was partitioned between EtOAc and H2O/brine mixture
  7. washThe EtOAc layer was washed with dilute aqueous HCl
  8. dry with materialaqueous NaHCO3, brine, dried with anhydrous Na2SO4
  9. customevaporated
  10. customThe resulting solid was chromatographed
  11. washeluting with CHCl3/MeOH
  12. customtriturated with a CHCl3 plus 40% EtOAc/hexane mixture

Sources & evidence

ORD record
ord-220c27a09a1146c29cf39249fc21ca41
Source dataset
uspto-grants-2016_04
Patent number
US09321721B2

Reaction notes

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