Sodium Iodide → [6-Chloro-1-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester

HRID 1631495Notes

Reaction equation

HRID 1631495 reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:15].[H-].[Na+].Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][C:22]=1[C:31]([F:34])([F:33])[F:32].[I-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[N:7]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][C:22]=2[C:31]([F:33])([F:32])[F:34])[C:6]=1[CH3:15]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 513420492-(Bromomethyl)-5-(methylsulphonyl)benzotrifluorideHCID 73013621methyl 2-(6-chloro-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

Product 1

HCID 86620148[6-Chloro-1-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred, ice-cooled solution of (6-chloro-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester (Example 99e) (0.03 g, 0.13 mmol) in DMF (1.0 ml) under an inert atmosphere of Argon is added sodium hydride (0.006 g of a 60% dispersion in mineral oil, 0.14 mmol). The reaction mixture is stirred at 0° C. for 45 minutes and then treated with 1-bromomethyl-4-methanesulfonyl-2-trifluoromethyl-benzene (Example 95a) (0.067 g, 0.21 mmol) followed by sodium iodide (0.031 g, 0.21 mmol). Stirring is continued at 0° C. for 2 hours and then the reaction mixture is poured onto water (15 ml) and extracted with DCM (5 ml). The organic portion is separated and concentrated in vacuo. The resulting crude is purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:8 increasing to 1:4) to yield the product which was further purified by trituration with ethyl acetate/iso-hexane to afford the titled product. (MH+ 475).

Workup

  1. stirringStirring
  2. waitis continued at 0° C. for 2 hours
  3. additionthe reaction mixture is poured onto water (15 ml)
  4. extractionextracted with DCM (5 ml)
  5. customThe organic portion is separated
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude is purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:8 increasing to 1:4)
  8. customto yield the product which
  9. customwas further purified by trituration with ethyl acetate/iso-hexane

Sources & evidence

ORD record
ord-549a15dd0dfa4afe8ac60331aad2cbf2
Source dataset
uspto-grants-2014_07
Patent number
US08791256B2

Reaction notes

Loading…