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

HRID 1754487Notes

Reaction equation

HRID 1754487 reaction equation
C[O:2][C:3](=[O:28])[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]([CH2:24][CH3:25])(=[O:23])=[O:22])=[CH:17][C:16]=2[Cl:26])[C:6]=1[CH3:27].COC(=O)CC1C2C(=NC=CC=2)NC=1C.[H-].[Na+].BrCC1C=CC(S(CC)(=O)=O)=CC=1Cl.[I-].[Na+]>CN(C=O)C>[Cl:26][C:16]1[CH:17]=[C:18]([S:21]([CH2:24][CH3:25])(=[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:28])=[O:2])=[C:6]1[CH3:27]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 67218699methyl 2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetateHCID 67219537[1-(2-Chloro-4-ethanesulfonyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl esterHCID 672198261-Bromomethyl-2-chloro-4-ethanesulfonyl-benzene

Product 1

HCID 11704178[1-(2-Chloro-4-ethanesulfonyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[1-(2-Chloro-4-ethanesulfonyl-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 ((2.68 g, 13.1 mmol) in dry DMF (95 ml) is added sodium hydride (577 mg of a 60% dispersion in mineral oil, 14.41 mmol). After stirring at room temperature for 1.5 hours, the reaction mixture is re-cooled to 0° C. and treated with 1-bromomethyl-2-chloro-4-ethanesulfonyl-benzene (6.6 g, 22.2 mmol) and sodium iodide (3.3 g, 22.2 mmol). The resulting mixture is stirred and allowed to warm to room temperature overnight. The reaction mixture is poured onto water (600 ml) and extracted with 1:1 ethyl acetate/diethyl ether (4×300 ml). The organic portions are washed with brine, dried (MgS04) and concentrated in vacuo and the resulting crude is purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:8 increasing to 1:2) to yield the titled product. (MH+421)

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 (600 ml)
  5. extractionextracted with 1:1 ethyl acetate/diethyl ether (4×300 ml)
  6. washThe organic portions are washed with brine
  7. customdried (MgS04)
  8. concentrationconcentrated in vacuo
  9. customthe resulting crude is purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:8 increasing to 1:2)

Sources & evidence

ORD record
ord-49e79bbf96954a6e9eae02c57ba94438
Source dataset
uspto-grants-2015_10
Patent number
US09169251B2

Reaction notes

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