Cesium carbonate → N-(3,4-Difluorobenzyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-6-(pyridin-2-yloxy)-1H-indole-3-carboxamide

HRID 40167

Reaction equation

HRID 40167 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][C:31]=1[F:32])[CH2:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=2)[N:11]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[C:10]=1[CH:26]([CH3:28])[CH3:27])=[O:8].C(=O)([O-])[O-].[Cs+].[Cs+].I[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=1>CN(C)C=O.[Cu]>[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][C:31]=1[F:32])[CH2:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([O:18][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=3)=[CH:15][CH:16]=2)[N:11]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[C:10]=1[CH:26]([CH3:28])[CH3:27])=[O:8]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2211262-IodopyridineHCID 59762365N-(3,4-Difluorobenzyl)-6-hydroxy-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide2×

Product 1

HCID 59762396N-(3,4-Difluorobenzyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-6-(pyridin-2-yloxy)-1H-indole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-(3,4-difluorobenzyl)-2-isopropyl-6-hydroxy-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide (Compound 220, 26 mg, 0.060 mmol) in dimethylformamide (1 ml) stirring at room temperature, was added cesium carbonate (83 mg, 0.25 mmol) and the reaction stirred for 5 minutes. 2-iodopyridine (0.05 mL, 0.09 g, 0.47 mmol) and then copper powder (7.0 mg, 0.11 mmol) was then directly added and the resulting mixture heated at 100° C. for 18 h. The reaction was cooled to room temperature, quenched with water, extracted with EtOAc, washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (50% EtOAc-hexanes, 100 % EtOAc) to yield the title compound as a white solid.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with water
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel (50% EtOAc-hexanes, 100 % EtOAc)

Sources & evidence

ORD record
ord-fe7ab3385e7e4a2188222dc5a2b9fb58
Source dataset
uspto-grants-2013_09
Patent number
US08524917B2

Linked notes

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