Potassium Carbonate → Methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate

HRID 396436Notes

Reaction equation

HRID 396436 reaction equation
[Cl:1][C:2]1[CH:13]=[CH:12][C:5](/[CH:6]=[CH:7]/[C:8]([O:10][CH3:11])=[O:9])=[C:4]([NH:14][S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:17])=[O:16])[CH:3]=1.Br.Br[CH2:26][C:27]([C:29]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][N:30]=1)=[O:28].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:11][O:10][C:8](=[O:9])[CH2:7][C:6]1[C:5]2[C:4](=[CH:3][C:2]([Cl:1])=[CH:13][CH:12]=2)[NH:14][C:26]=1[C:27]([C:29]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][N:30]=1)=[O:28].[CH3:11][O:10][C:8](=[O:9])[CH2:7][CH:6]1[C:5]2[C:4](=[CH:3][C:2]([Cl:1])=[CH:13][CH:12]=2)[N:14]([S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:16])=[O:17])[CH:26]1[C:27]([C:29]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][N:30]=1)=[O:28]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11371593Methyl trans-4-chloro-2-(phenylsulfonylamino)cinnamateHCID 230033492-Bromo-1-(4-chloro-pyridin-2-yl)-ethanone hydrobromide

Product 2

HCID 23003320Methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetateYield 28%HCID 23003437Methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1-(phenylsulfonyl)indolin-3-yl]acetateYield 27%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of methyl trans-4-chloro-2-(phenylsulfonylamino)cinnamate (step 1 of Example 8, Method A, 675 mg, 1.92 mmol), 2-bromoacetyl-4-chloropyridine hydrobromide* (907 mg, 2.88 mmol), and potassium carbonate (2.65 g, 19.18 mmol) in acetone (20 ml) was heated at reflux temperature for 4 h. The mixture was cooled and concentrated. The residue was diluted with ethyl acetate (150 ml) and washed with water (70 ml×6). After drying (MgSO4) and removal of solvent, the crude product was purified by flash column chromatography eluting with ethyl acetate/hexane (1:6-1:3) to afford 195 mg (28%) of the title compound (yellow solids) along with 264 mg (27%) of methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1-(phenylsulfonyl)indolin-3-yl]acetate (brown crystals).

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 4 h
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated
  5. additionThe residue was diluted with ethyl acetate (150 ml)
  6. washwashed with water (70 ml×6)
  7. customAfter drying
  8. custom(MgSO4) and removal of solvent
  9. customthe crude product was purified by flash column chromatography
  10. washeluting with ethyl acetate/hexane (1:6-1:3)

Sources & evidence

ORD record
ord-3691e35e222c4fbdbb64ebd012e1dc28
Source dataset
uspto-grants-2003_08
Patent number
US06608070B1

Reaction notes

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