Hexane → 5-bromo-3-[1-(2,6-dichloro-3-fluorophenyl)-2-fluoro-2,2-bis(phenylsulfonyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 2095743Notes

Reaction equation

HRID 2095743 reaction equation
[F:1][CH:2]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13])[S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:5])=[O:4].[Li]CCCC.CCCCCC.[Br:32][C:33]1[CH:34]=[C:35]2[C:41]([CH:42]([C:44]3[C:49]([Cl:50])=[CH:48][CH:47]=[C:46]([F:51])[C:45]=3[Cl:52])O)=[CH:40][NH:39][C:36]2=[N:37][CH:38]=1.S(Cl)(Cl)=O>C1COCC1.C(Cl)Cl>[C:15]1([S:12]([C:2]([S:3]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)(=[O:5])=[O:4])([F:1])[CH:42]([C:41]2[C:35]3[C:36](=[N:37][CH:38]=[C:33]([Br:32])[CH:34]=3)[NH:39][CH:40]=2)[C:44]2[C:49]([Cl:50])=[CH:48][CH:47]=[C:46]([F:51])[C:45]=2[Cl:52])(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 5

HCID 8058HexaneHCID 24386Thionyl ChlorideHCID 16079185Fluorobis(phenylsulfonyl)methaneHCID 67004517(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)(2,6-dichloro-3-fluorophenyl)methanolHCID 178418339Butyllithium

Product 1

HCID 866593275-bromo-3-[1-(2,6-dichloro-3-fluorophenyl)-2-fluoro-2,2-bis(phenylsulfonyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 1-(fluoro(phenylsulfonyl)methylsulfonyl)benzene (836 mg, 2.66 mmol) in THF (8.0 mL) was added 2.5 M of n-BuLi in Hexane (1.18 mL, 2.95 mmol) at −78° C.; the resulting mixture was stirred for 30 min at −78° C. before use. To a stirred solution of (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-(2,6-dichloro-3-fluorophenyl)methanol (250.0 mg, 0.6410 mmol) in THF (5.0 mL, 62 mmol) was added thionyl chloride (0.12 mL, 1.6 mmol) at 0° C. The resulting mixture was stirred for 30 min at rt, then the solvent was removed and the residue was dried under high vacuum. To this residue was added THF (10.0 mL) followed by adding the previously prepared solution (lithiated 1-(fluoro(phenylsulfonyl)methylsulfonyl)benzene) by canula at −78° C. The resulting mixture was allowed to warm up to rt in about 1 hr. Then the solvent was removed under reduced pressure to give a residue, which was diluted by DCM and extracted by DCM (20 mL×3). The organic phase were combined, dried (Na2SO4) and concentrated to give a crude residue, which was purified by silica gel chromatography (eluent: 20% AcOEt in DCM) to give the title compound. MS (ES+): m/z 684.92, 686.92, 688.92 [MH+]. HPLC: tR=1.65 min (polar—3 min, TOF)

Workup

  1. stirringThe resulting mixture was stirred for 30 min at rt
  2. customthe solvent was removed
  3. customthe residue was dried under high vacuum
  4. additionTo this residue was added THF (10.0 mL)
  5. additionby adding the previously prepared solution (lithiated 1-(fluoro(phenylsulfonyl)methylsulfonyl)benzene) by canula at −78° C
  6. temperatureto warm up to rt in about 1 hr
  7. customThen the solvent was removed under reduced pressure
  8. customto give a residue, which
  9. extractionextracted by DCM (20 mL×3)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customto give a crude residue, which
  13. customwas purified by silica gel chromatography (eluent: 20% AcOEt in DCM)

Sources & evidence

ORD record
ord-ec6cab6a8c9d42d3abfde4f98b7e2bbe
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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