Sodium hydride → 1-benzenesulfonyl-2-{[cyanomethyl(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester

HRID 1888384Notes

Reaction equation

HRID 1888384 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C:6]=1[CH2:23]Br)=[O:4].[C:25]([CH2:27][NH:28][S:29]([C:32]1[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=1)(=[O:31])=[O:30])#[N:26].[H-].[Na+]>C1COCC1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C:6]=1[CH2:23][N:28]([CH2:27][C:25]#[N:26])[S:29]([C:32]1[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=1)(=[O:31])=[O:30])=[O:4]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 3113400N-Cyanomethyl-4-methyl-benzenesulfonamideHCID 582663361-Benzenesulfonyl-2-bromomethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester

Product 1

HCID 582667731-benzenesulfonyl-2-{[cyanomethyl(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl esterYield 80%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) mixture of 1-benzenesulfonyl-2-bromomethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (1.64 g, 4.00 mmol) and N-cyanomethyl-4-methyl-benzenesulfonamide (0.93 g, 4.40 mmol) in dry THF (10 mL) was added sodium hydride (0.176 g, 60% dispersion in mineral oil, 4.40 mmol) in two equal portions. The reaction mixture was stirred at 0° C. for 15 minutes then allowed to warm to room temperature. After 66 h the reaction mixture was diluted with DCM (60 mL) and saturated aqueous sodium carbonate solution (25 mL). The layers were separated and the aqueous phase was extracted with DCM (2×25 mL). The combined organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was triturated with THF (5 mL) and the resultant solid dried in vacuo to afford the title compound as a beige solid (1.72 g, 80%). LCMS (Method B): RT=3.91 min, M+H+=539.

Workup

  1. temperatureTo a cooled
  2. temperatureto warm to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with DCM (2×25 mL)
  5. dry with materialThe combined organic phase was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was triturated with THF (5 mL)
  8. customthe resultant solid dried in vacuo

Sources & evidence

ORD record
ord-fc6577fa523e4caba78b663855cfe705
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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