4-Toluenesulfonyl chloride → 4-Chloro-3-iodo-1-(4-methylbenzene-1-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

HRID 490274Notes

Reaction equation

HRID 490274 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[NH:10][CH:11]=[C:12]([I: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.C([O-])(O)=O.[Na+]>C(OCC)(=O)C.C1COCC1>[Cl:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[N:10]([S:20]([C:17]3[CH:18]=[CH:19][C:14]([CH3:24])=[CH:15][CH:16]=3)(=[O:22])=[O:21])[CH:11]=[C:12]([I:13])[C:5]=12

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 115508744-Chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 534382524-Chloro-3-iodo-1-(4-methylbenzene-1-sulfonyl)-1H-pyrrolo[2,3-b]pyridineYield 60%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Under protective gas atmosphere (argon), 63.5 g (1.59 mol) of sodium hydride were suspended in 1000 ml of abs. THF. To this were added dropwise with cooling at a temperature of 0-5° C. a solution of 402 g (1.44 mol) of 4-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine in 3000 ml of abs. THF, and the reaction mixture was left to stir for a further 15 minutes after completion of addition. Subsequently, 358 g (1.88 mol) of p-toluenesulphonyl chloride were added in portions to the reaction mixture in such a way that the temperature was kept between 5-10° C. After the addition had ended, the mixture was allowed to come to 20° C. and stirred at this temperature for a further hour. On completion of conversion (TLC monitoring of conversion), the reaction mixture was admixed with 20 l of saturated NaHCO3 solution and 10 l of ethyl acetate, and extracted, and the organic phase was removed. The aqueous phase was extracted twice more with 10 l each time of ethyl acetate, and the organic phases were combined, dried and freed of volatile constituents in a water-jet vacuum. To purify the crystalline crude product, it was taken up in dichloromethane and chromatographed using silica gel (CH2Cl2: 40/60 petroleum ether=3:7). After the solvents had been removed, the crystal slurry was extractively stirred in diethyl ether, and the solids were filtered off with suction and dried at 20° C. under high vacuum. A total of 372 g (0.86 mol, 60%) of 4-chloro-1-(toluene-4-sulphonyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine were isolated as a colourless solid.

Workup

  1. additionTo this were added dropwise
  2. additionafter completion of addition
  3. customwas kept between 5-10° C
  4. additionAfter the addition
  5. customto come to 20° C.
  6. stirringstirred at this temperature for a further hour
  7. extractionextracted
  8. customthe organic phase was removed
  9. extractionThe aqueous phase was extracted twice more with 10 l each time of ethyl acetate
  10. customdried
  11. customTo purify the crystalline crude product, it
  12. customchromatographed
  13. customAfter the solvents had been removed
  14. stirringthe crystal slurry was extractively stirred in diethyl ether
  15. filtrationthe solids were filtered off with suction
  16. customdried at 20° C. under high vacuum

Sources & evidence

ORD record
ord-e3a64129996f42a9b3b812073fcc0b4c
Source dataset
uspto-grants-2009_05
Patent number
US07528146B2

Reaction notes

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