4-Toluenesulfonyl chloride → HCID 67003430, compound

HRID 1521988Notes

Reaction equation

HRID 1521988 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:9]([Cl:10])=[CH:8][N:7]=[C:6]2[NH:11][CH:12]=[CH:13][C:5]=12.[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1>CN(C)C=O>[Cl:3][C:4]1[C:9]([Cl:10])=[CH:8][N:7]=[C:6]2[N:11]([S:20]([C:17]3[CH:18]=[CH:19][C:14]([CH3:24])=[CH:15][CH:16]=3)(=[O:22])=[O:21])[CH:12]=[CH:13][C:5]=12

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chloride2×HCID 24758Sodium hydrideHCID 467379024,5-Dichloro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 67003430HCID 67003430, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To 60% sodium hydride in mineral oil (1.390 g, 34.8 mmol) in N,N-dimethylformamide (60 mL) at 0° C. was added a solution of 4,5-dichloro-1H-pyrrolo[2,3-b]pyridine (Adesis, 5.0 g, 26.7 mmol) in N,N-dimethylformamide (20 mL) slowly over 5 minutes. The mixture was allowed to warm to room temperature and was stirred for 30 minutes. The mixture was cooled to 0° C. and a solution of p-toluenesulfonyl chloride (5.35 g, 28.1 mmol) in N,N-dimethylformamide (20 mL) was added. The mixture was allowed to warm to room temperature and stirred for 2 hours. Additional p-toluenesulfonyl chloride (500 mg, 2.62 mmol) was added, and the mixture was stirred another 1 hour at room temperature. The reaction was quenched with saturated aqueous ammonium chloride (25 mL) and extracted with ethyl acetate (twice). The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (AnaLogix IntelliFlash 280) eluting with a gradient of 40-70% ethyl acetate in hexanes to afford the title compound. MS (ESI+) m/z 341.6 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 2 hours
  4. stirringthe mixture was stirred another 1 hour at room temperature
  5. customThe reaction was quenched with saturated aqueous ammonium chloride (25 mL)
  6. extractionextracted with ethyl acetate (twice)
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography on silica gel (AnaLogix IntelliFlash 280)
  12. washeluting with a gradient of 40-70% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3c816161a8054211985fe86b464d539b
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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