HCID 59683257, compound → HCID 59683267, compound

HRID 447772Notes

Reaction equation

HRID 447772 reaction equation
[F:1][C:2]1[C:7]([F:8])=[C:6]([CH3:9])[CH:5]=[C:4](I)[C:3]=1[NH:11][C:12]([NH:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=[O:13]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:1][C:2]1[C:3]2[NH:11][C:12](=[O:13])[N:14]([CH:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[C:4]=2[CH:5]=[C:6]([CH3:9])[C:7]=1[F:8]

Participants

5

Reactant 1

HCID 59683257HCID 59683257, compound2×

Product 1

HCID 59683267HCID 59683267, compound

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

1,1-dimethylethyl 4-({[(2,3-difluoro-6-iodo-4-methylphenyl)amino]carbonyl}amino)-1-piperidine-carboxylate D21 was dissolved in 1 ml dioxan. Under an argon atmosphere, a mixture of 1,4-dioxane (3 ml), Pd2 dba3 (35 mg, 0.4 mmol), NatBuO (120 mg, 1.20 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (21 mg, 0.4 mmol) was stirred for 10 minutes at room temperature and then 1,1-dimethylethyl 4-({[(2,3-difluoro-6-iodo-4-methylphenyl)amino]carbonyl}amino)-1-piperidine-carboxylate D21 (300 mg) was added and the mixture heated at 80° C. for 2 h. The reaction mixture was cooled to room temperature, quenched with NH4Cl (saturated solution) and extracted with ethyl acetate, Drying (MgSO4), evaporation, and crystallisation from diethyl ether gave 150 mg of the title compound. M−−H=366.

Workup

  1. temperaturethe mixture heated at 80° C. for 2 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with NH4Cl (saturated solution)
  4. extractionextracted with ethyl acetate
  5. customDrying
  6. custom(MgSO4), evaporation, and crystallisation from diethyl ether

Sources & evidence

ORD record
ord-84f0cc68de9e4cfdbf81f674e609793d
Source dataset
uspto-grants-2013_07
Patent number
US08481566B2

Reaction notes

Loading…