Iodine → 4-Chloro-5-fluoro-2-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1521996Notes

Reaction equation

HRID 1521996 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]2[N:9]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)(=[O:14])=[O:13])[CH:10]=[CH:11][C:3]=12.C([N-]C(C)C)(C)C.[Li+].O1CCCC1.CCCCCCC.C(C1C=CC=CC=1)C.[I:49]I>O1CCCC1>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]2[N:9]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:10]([I:49])=[CH:11][C:3]=12

Participants

6

Reactant 4

HCID 807IodineHCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzolHCID 497616281-(Benzenesulfonyl)-4-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 904139044-Chloro-5-fluoro-2-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of Example 231A (3.560 g, 11.46 mmol) in tetrahydrofuran (75 mL) at 78° C. was added dropwise 2M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (11.46 mL, 22.91 mmol). The mixture was stirred at −78° C. for 30 minutes and iodine (5.82 g, 22.91 mmol) in tetrahydrofuran (25 mL) was added. After stirring at −78° C. for 3 hours, the reaction was quenched with aqueous sodium thiosulfate and extracted with ethyl acetate (twice). The combined organic layers were dried over magnesium sulfate, filtered, concentrated until most solvent was removed. The suspension was diluted with ethyl acetate and warmed with a heat gun. Heptanes were added to the suspension and the mixture was stirred for 1 hour. The solid was filtered, washed with heptanes/ethyl acetate (1:1), and vacuum oven-dried to give the title compound. The filtrate was concentrated and triturated with heptanes/ethyl acetate (1:1) to give additional title compound. MS (ESI+) m/z 436.9 (M+H)+.

Workup

  1. stirringAfter stirring at −78° C. for 3 hours
  2. customthe reaction was quenched with aqueous sodium thiosulfate
  3. extractionextracted with ethyl acetate (twice)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated until most solvent
  7. customwas removed
  8. additionThe suspension was diluted with ethyl acetate
  9. temperaturewarmed with a heat gun
  10. additionHeptanes were added to the suspension
  11. stirringthe mixture was stirred for 1 hour
  12. filtrationThe solid was filtered
  13. washwashed with heptanes/ethyl acetate (1:1), and vacuum
  14. customoven-dried

Sources & evidence

ORD record
ord-cd09dc8bd68b48039e6c50b5db4897f0
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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