Sodium hydride → 1-benzenesulfonyl-5-bromo-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester

HRID 1505852Notes

Reaction equation

HRID 1505852 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Br:16])[CH:14]=2)[N:9]([S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)(=[O:19])=[O:18])[C:8]=1[CH2:26]Br)=[O:6].[C:28]([CH2:30][NH:31][S:32]([C:35]1[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=1)(=[O:34])=[O:33])#[N:29]>C1COCC1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+].O>[CH3:3][O:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Br:16])[CH:14]=2)[N:9]([S:17]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)(=[O:18])=[O:19])[C:8]=1[CH2:26][N:31]([CH2:30][C:28]#[N:29])[S:32]([C:35]1[CH:36]=[CH:37][C:38]([CH3:41])=[CH:39][CH:40]=1)(=[O:34])=[O:33])=[O:6]

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 3113400N-Cyanomethyl-4-methyl-benzenesulfonamideHCID 582663771H-Pyrrolo[2,3-b]pyridine-3-carboxylic acid, 5-bromo-2-(bromomethyl)-1-(phenylsulfonyl)-, methyl ester

Product 1

HCID 582666181-benzenesulfonyl-5-bromo-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl esterYield 82.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (48 mg, 60% dispersion in mineral oil, 12.0 mmol) was added to a cooled (0° C.) mixture of 1-benzenesulfonyl-5-bromo-2-bromomethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (0.56 g, 1.16 mmol) and N-cyanomethyl-4-methyl-benzenesulfonamide (0.25 g, 1.20 mmol) in dry THF (3.5 mL). The reaction mixture was stirred at 0° C. for 15 minutes, then allowed to warm to ambient temperature and stirred for 18 h. The reaction mixture was then diluted with DCM (40 mL), saturated aqueous sodium carbonate solution (20 mL) and water (20 mL). The organic phase was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash column chromatography (silica, 5 g cartridge, Si-SPE, DCM) to afford the title compound as a beige solid (0.59 g, 80%). LCMS (Method B): RT=4.28 min, M+H+=617/619.

Workup

  1. temperaturea cooled
  2. temperatureto warm to ambient temperature
  3. stirringstirred for 18 h
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified by flash column chromatography (silica, 5 g cartridge, Si-SPE, DCM)

Sources & evidence

ORD record
ord-39ef4c8a6cec4857b964ad8ac8aab0a7
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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