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

HRID 2240255Notes

Reaction equation

HRID 2240255 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]pyridine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

Under an atmosphere of protective gas (argon), 63.5 g (1.59 mol) of sodium hydride are suspended in 1000 ml of abs. THF. 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 is added dropwise, and the reaction mixture is, after the end of the addition, allowed to stir for 15 minutes. 358 g (1.88 mol) of p-toluenesulfonyl chloride are added a little at a time to the reaction mixture, so that the temperature is kept between 5 and 10° C. After the end of the addition, the mixture is allowed to warm to 20° C. and stirred at this temperature for another hour. After complete conversion (the conversion is monitored by TLC), 20 l of saturated sodium bicarbonate solution and 10 l of ethyl acetate are added to the reaction mixture, the mixture is extracted and the organic phase is separated off. The aqueous phase is reextracted two more times with in each case 10 l of ethyl acetate and the organic phases are combined, dried and, under water pump vacuum, freed from volatile components. For purification of the crystalline crude product, the product is taken up in dichloromethane and chromatographed on silica gel (dichloromethane:petroleum ether=3:7). The solvents are removed under reduced pressure and the crystal slurry is triturated with diethyl ether, filtered off with suction and dried at 20° C. under high vacuum. 372 g (60% of theory) of the title compound are isolated as a solid.

Workup

  1. additionafter the end of the addition
  2. customis kept between 5 and 10° C
  3. additionAfter the end of the addition
  4. temperatureto warm to 20° C.
  5. stirringstirred at this temperature for another hour
  6. additionare added to the reaction mixture
  7. extractionthe mixture is extracted
  8. customthe organic phase is separated off
  9. customdried and, under water pump vacuum
  10. customFor purification of the crystalline crude product
  11. customchromatographed on silica gel (dichloromethane:petroleum ether=3:7)
  12. customThe solvents are removed under reduced pressure
  13. customthe crystal slurry is triturated with diethyl ether
  14. filtrationfiltered off with suction
  15. customdried at 20° C. under high vacuum

Sources & evidence

ORD record
ord-b43cb38567724dd6bbb14e1602abf357
Source dataset
uspto-grants-2010_05
Patent number
US07723347B2

Reaction notes

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