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

HRID 1754483Notes

Reaction equation

HRID 1754483 reaction equation
C[O:2][C:3](=[O:27])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][C:16]=2[Cl:25])[C:6]=1[CH3:26].COC(=O)CC1C2C(=NC=CC=2)NC=1C.[H-].[Na+].BrCC1C=CC(S(C)(=O)=O)=CC=1Cl.[I-].[Na+]>CN(C=O)C>[Cl:25][C:16]1[CH:17]=[C:18]([S:21]([CH3:24])(=[O:22])=[O:23])[CH:19]=[CH:20][C:15]=1[CH2:14][N:7]1[C:8]2=[N:9][CH:10]=[CH:11][CH:12]=[C:13]2[C:5]([CH2:4][C:3]([OH:27])=[O:2])=[C:6]1[CH3:26]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 27610831-(Bromomethyl)-2-chloro-4-(methylsulfonyl)benzeneHCID 67218699methyl 2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetateHCID 67218985[1-(2-Chloro-4-methanesulfonyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester

Product 1

HCID 11618108[1-(2-Chloro-4-methanesulfonyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[1-(2-Chloro-4-methanesulfonyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester: 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-9c6b1e1b90cd4d58a32fbcc11736bd98
Source dataset
uspto-grants-2015_10
Patent number
US09169251B2

Reaction notes

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