Iodine → 5-chloro-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde

HRID 1968231Notes

Reaction equation

HRID 1968231 reaction equation
[Cl:1][C:2]1[CH:7]=[N:6][C:5]2[NH:8][CH:9]=[CH:10][C:4]=2[C:3]=1[CH:11]=[O:12].[I:13]I.[I-].[Na+].[OH-].[Na+].[H-].[Na+].[S:21](Cl)([C:24]1[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=1)(=[O:23])=[O:22]>CCO.O.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[N:6][C:5]2[N:8]([S:21]([C:24]3[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:9]=[C:10]([I:13])[C:4]=2[C:3]=1[CH:11]=[O:12]

Participants

10

Reactant 6

HCID 807IodineHCID 5238Sodium IodideHCID 73974-Toluenesulfonyl chlorideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 242292805-Chloro-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde

Product 1

HCID 582934415-chloro-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbaldehydeYield 70.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-chloro-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde (5.0 g, 27.7 mmol) in EtOH (100 mL) was added iodine (8.43 g, 33.2 mmol), sodium iodide (4.98 g, 33.2 mmol), and aqueous NaOH (1N, 35 mL, 35 mmol). After stirring for 4 h at room temperature, the reaction mixture was diluted with water (200 mL). An orange precipitate was collected by filtration and dried under vacuum. The solid was dissolved in DMF (60 mL) and sodium hydride (60%, 1.33 g, 33.2 mmol) was slowly added. The deep red solution was stirred for 30 min at room temperature. Tosyl chloride (5.81 g, 30.5 mmol) was added and the mixture was stirred at room temperature for 2 h. The mixture was diluted with EtOAc and the reaction was quenched with water. The organics were separated, washed with aqueous NaHSO3 (0.1 N) and brine, dried over MgSO4, and concentrated. Purification by silica gel chromatography (3:1:1 hexane/DCM/EtOAc) gave the title compound as a yellow solid (8.96 g, 70%). 1H NMR (500 MHz, DMSO-d6) δ 3.15 (s, 3 H), 8.24 (d, J=8.5 Hz, 2 H), 8.81 (d, J=8.5 Hz, 2 H), 9.17 (s, 1 H), 9.38 (s, 1 H), 11.81 (s, 1 H). [M+H] calc'd for C15H10ClIN2O3S, 461, 463; found, 461, 463.

Workup

  1. filtrationAn orange precipitate was collected by filtration
  2. customdried under vacuum
  3. dissolutionThe solid was dissolved in DMF (60 mL)
  4. stirringThe deep red solution was stirred for 30 min at room temperature
  5. stirringthe mixture was stirred at room temperature for 2 h
  6. customthe reaction was quenched with water
  7. customThe organics were separated
  8. washwashed with aqueous NaHSO3 (0.1 N) and brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customPurification by silica gel chromatography (3:1:1 hexane/DCM/EtOAc)

Sources & evidence

ORD record
ord-dafeb79f47ff419fa684d5d6abd18c2b
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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