Sodium hydride → 1H-Pyrrolo[2,3-b]pyridine-3acetic acid,1-[(4-cyano-3-ethoxyphenyl)sulfonyl]-2-methyl-,methyl ester

HRID 1631513Notes

Reaction equation

HRID 1631513 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:17])[CH2:6][C:7]1[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8]=1[CH3:16].[C:18]([C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][C:21]=1[O:30][CH2:31][CH3:32])#[N:19]>C1COCC1.C1COCC1.CN(C=O)C>[CH3:3][O:4][C:5](=[O:17])[CH2:6][C:7]1[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[N:9]([S:26]([C:23]2[CH:24]=[CH:25][C:20]([C:18]#[N:19])=[C:21]([O:30][CH2:31][CH3:32])[CH:22]=2)(=[O:28])=[O:27])[C:8]=1[CH3:16]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 552808794-Cyano-3-ethoxybenzene-1-sulfonyl chlorideHCID 67218699methyl 2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

Product 1

HCID 672193091H-Pyrrolo[2,3-b]pyridine-3acetic acid,1-[(4-cyano-3-ethoxyphenyl)sulfonyl]-2-methyl-,methyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred, ice-cooled (0° C.) suspension of sodium hydride (26.3 mg of a 60% dispersion in mineral oil, 0.686 mmol) in dry THF (10 ml) under an inert atmosphere of Argon is added dropwise (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester ((0.1 g, 0.49 mmol) in THF/DMF (4 ml of a 3:1 mixture). The reaction mixture is stirred at 0° C. for 1 hour and then treated with 4-cyano-3-ethoxy-benzenesulfonyl chloride (168 mg, 0.686 mmol) in dry THF (1 ml). Stirring continued at 0° C. for 10 minutes and at room temperature for 10 minutes and then the reaction mixture is poured onto water (50 ml). The mixture is extracted with ethyl acetate (2×50 ml) and the organic portions are combined, washed brine (50 ml), dried (MgSO4) and concentrated in vacuo. The resulting crude is purified by chromatography on silica eluting with iso-hexane/ethyl acetate (0%-20% ethyl acetate) to yield the titled product. (MH+ 414).

Workup

  1. temperatureTo a stirred, ice-cooled
  2. stirringStirring
  3. waitcontinued at 0° C. for 10 minutes and at room temperature for 10 minutes
  4. additionthe reaction mixture is poured onto water (50 ml)
  5. extractionThe mixture is extracted with ethyl acetate (2×50 ml)
  6. washwashed brine (50 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting crude is purified by chromatography on silica eluting with iso-hexane/ethyl acetate (0%-20% ethyl acetate)

Sources & evidence

ORD record
ord-5bd7929736384e91852d51c7628c22ce
Source dataset
uspto-grants-2014_07
Patent number
US08791256B2

Reaction notes

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