1,1-Dimethylethyl 4-({[(2-fluoro-6-iodo-4-methylphenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate → 1,1-Dimethylethyl 4-(4-fluoro-6-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

HRID 447754Notes

Reaction equation

HRID 447754 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4](I)[C:3]=1[NH:10][C:11]([NH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[O:12]>[Cl-].[Cl-].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].[Pd+2].O1CCOCC1>[F:1][C:2]1[C:3]2[NH:10][C:11](=[O:12])[N:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:4]=2[CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

4

Reactant 1

HCID 596832811,1-Dimethylethyl 4-({[(2-fluoro-6-iodo-4-methylphenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate

Product 1

HCID 596832531,1-Dimethylethyl 4-(4-fluoro-6-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 2

HCID 178478645Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Under an argon atmosphere, a mixture of 1,4-dioxane (3 ml), palladium 1,1′-bis(diphenylphosphino)ferrocene dichloride (10% mol, 0.0623 mmol, ˜x50 mg), NatBuO (2 eq., 1.26 mmol, 121 mg), were sonicated for 10 minutes at room temperature and 1,1-dimethylethyl 4-({[(2-fluoro-6-iodo-4-methylphenyl)amino]carbonyl}amino)-1-piperidine-carboxylate (D3) (1 eq., 0.623 mmol, 300 mg) was added at room temperature and the mixture was refluxed at 80° C. for one overnight. The reaction mixture was cooled to room temperature, poured onto NH4Cl (saturated solution) and the aqueous solution obtained was extracted with ethyl acetate repeatedly; the organics were combined, dried over Na2SO4, filtered and the solvent was evaporated to afford the crude compound (250 mg) that was purified by MDAP to yield the title compound, 30 mg, 11%.

Workup

  1. customwere sonicated for 10 minutes at room temperature
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionpoured onto NH4Cl (saturated solution)
  4. customthe aqueous solution obtained
  5. extractionwas extracted with ethyl acetate repeatedly
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customto afford the crude compound (250 mg) that
  10. customwas purified by MDAP

Sources & evidence

ORD record
ord-dc99d3a1c3154514be6a609ff929eb1e
Source dataset
uspto-grants-2013_07
Patent number
US08481566B2

Reaction notes

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