Water → HCID 21906238, compound

HRID 1247157Notes

Reaction equation

HRID 1247157 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH:16][C:17]2[CH:32]=[CH:31][C:30](I)=[CH:29][C:18]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=2)=[O:20])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[OH2:41].CN(C)[CH:44]=[O:45]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH:16][C:17]2[CH:32]=[CH:31][C:30]([C:44]([OH:45])=[O:41])=[CH:29][C:18]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=2)=[O:20])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 8471TriethylamineHCID 219066352-[(1-tert-butoxycarbonylpiperidin-4-ylcarbonyl)amino]-N-(5-chloropyridin-2-yl)-5-iodobenzamide

Product 1

HCID 21906238HCID 21906238, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
60 °C

Procedure

To a stirring solution of 2-[(1-tert-butoxycarbonylpiperidin-4-ylcarbonyl)amino]-N-(5-chloropyridin-2-yl)-5-iodobenzamide (0.51 g, 0.88 mmol) in N,N-dimethylformamide (13 mL) under argon was added dichlorobis(triphenylphosphine)palladium(II) (28 mg, 0.04 mmol) and triethylamine (0.5 mL, 3.5 mmol) followed by water (3 mL). The reaction mixture was evacuated and placed under an atmosphere of carbon monoxide, heated at 60° C. for 3 h., and concentrated in vacuo. The resulting residue was partitioned between aqueous sodium bicarbonate and ethyl acetate and the layers separated. The aqueous phase was treated with a small amount of dichloromethane and then solid citric acid to pH 3. The resulting mixture was extracted with 3:1 chloroform:isopropanol. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified by chromatography over silica gel, eluting with 2:4:0.5 ethyl acetate:toluene:acetic acid. The chromatography product was slurried in diethyl ether and filtered to give 0.31 g (69%) of a yellow solid.

Workup

  1. customThe reaction mixture was evacuated
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was partitioned between aqueous sodium bicarbonate and ethyl acetate
  4. customthe layers separated
  5. additionThe aqueous phase was treated with a small amount of dichloromethane
  6. extractionThe resulting mixture was extracted with 3:1 chloroform
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by chromatography over silica gel
  11. washeluting with 2:4:0.5 ethyl acetate
  12. filtrationfiltered

Sources & evidence

ORD record
ord-882c189885ca47758c36dd649851804f
Source dataset
uspto-grants-2006_10
Patent number
US07129245B2

Reaction notes

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