Sodium Iodide → [1-(2-Chloro-4-methanesulfonyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester

HRID 1445599Notes

Reaction equation

HRID 1445599 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:14].[H-].[Na+].Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][C:21]=1[Cl:30].[I-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:27])=[O:28])=[CH:22][C:21]=2[Cl:30])[C:6]=1[CH3:14]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 27610831-(Bromomethyl)-2-chloro-4-(methylsulfonyl)benzeneHCID 67218699methyl 2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

Product 1

HCID 67218985[1-(2-Chloro-4-methanesulfonyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice cooled (0° C.) stirred solution of (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester ((2.25 g, 1.1 mmol) in dry DMF (15 ml) is added sodium hydride (0.484 g of a 60% dispersion in mineral oil, 12.1 mmol). After stirring at room temperature for 3 hours, the reaction mixture is re-cooled to 0° C. and treated with 1-bromomethyl-2-chloro-4-methanesulfonyl-benzene (5.0 g, 17.6 mmol) and sodium iodide (2.64 g, 17.6 mmol). The resulting mixture is stirred and allowed to warm to room temperature overnight. The reaction mixture is poured onto water (300 ml) and extracted with 1:1 ethyl acetate/diethyl ether. The organic portions are washed with brine, dried (Na2SO4) and concentrated in vacuo and the resulting crude is purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:4 increasing to 1:2) to yield the titled product. (MH+ 407)

Workup

  1. temperaturethe reaction mixture is re-cooled to 0° C.
  2. stirringThe resulting mixture is stirred
  3. temperatureto warm to room temperature overnight
  4. additionThe reaction mixture is poured onto water (300 ml)
  5. extractionextracted with 1:1 ethyl acetate/diethyl ether
  6. washThe organic portions are washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customthe resulting crude is purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:4 increasing to 1:2)

Sources & evidence

ORD record
ord-8e8675bb71784a54bc2e56f8439ed571
Source dataset
uspto-grants-2010_02
Patent number
US07666878B2

Reaction notes

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