Iodine → 1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclobutyl-1-(4-methylsulfanyl-phenyl)-ethanol

HRID 1515699Notes

Reaction equation

HRID 1515699 reaction equation
[Mg].II.Br[CH2:5][CH:6]1[CH2:9][CH2:8][CH2:7]1.[C:10]1([S:16]([N:19]2[C:23]3=[N:24][CH:25]=[C:26]([F:28])[CH:27]=[C:22]3[CH:21]=[C:20]2[C:29]([C:31]2[CH:36]=[CH:35][C:34]([S:37][CH3:38])=[CH:33][CH:32]=2)=[O:30])(=[O:18])=[O:17])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>O1CCCC1>[C:10]1([S:16]([N:19]2[C:23]3=[N:24][CH:25]=[C:26]([F:28])[CH:27]=[C:22]3[CH:21]=[C:20]2[C:29]([C:31]2[CH:32]=[CH:33][C:34]([S:37][CH3:38])=[CH:35][CH:36]=2)([OH:30])[CH2:5][CH:6]2[CH2:9][CH2:8][CH2:7]2)(=[O:17])=[O:18])[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 807IodineHCID 2734658(Bromomethyl)cyclobutane2×HCID 5462224MagnesiumHCID 67228557(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-phenyl)-methanone

Product 1

HCID 672287211-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclobutyl-1-(4-methylsulfanyl-phenyl)-ethanolYield 26.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of magnesium powder (1.6 g, 67.5 mmol) and iodine (3 pieces) in dry tetrahydrofuran (8 mL) was added (bromomethyl)cyclobutane (1.1 mL, 7.5 mmol) dropwise at room temperature. After the reaction initiated, a solution of (bromomethyl)cyclobutane (5.5 mL, 37.5 mmol) in dry tetrahydrofuran (30 mL) was added dropwise and then heated at reflux for 30 min. The resulting Grignard reagent was added to a solution of (1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-phenyl)-methanone (1.9 g, 4.5 mmol) at 0° C. and stirred for 1 h. The reaction was quenched with water, extracted with ethyl acetate (300 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 15% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclobutyl-1-(4-methylsulfanyl-phenyl)-ethanol (600 mg, 26.9%) as a light yellow solid; LC/MS m/e calcd for C26H25FN2O3S2 [M+H]+ 497.63, observed 496.8.

Workup

  1. temperatureheated
  2. temperatureat reflux for 30 min
  3. customThe reaction was quenched with water
  4. extractionextracted with ethyl acetate (300 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f2aad80bf2ae4c07915b7a8811a26b7d
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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