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

HRID 1515882Notes

Reaction equation

HRID 1515882 reaction equation
C1(S([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[C:19]([C:21]2[CH:26]=[CH:25][C:24]([S:27][CH3:28])=[CH:23][CH:22]=2)=[O:20])(=O)=O)C=CC=CC=1.[Mg].Br[CH2:31][CH:32]1[CH2:35][CH2:34][CH2:33]1.II>O1CCCC1.[Cl-].[Na+].O>[CH:32]1([CH2:31][C:19]([C:21]2[CH:22]=[CH:23][C:24]([S:27][CH3:28])=[CH:25][CH:26]=2)([C:11]2[NH:10][C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=2)[OH:20])[CH2:35][CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 807IodineHCID 2734658(Bromomethyl)cyclobutaneHCID 5462224MagnesiumHCID 67227743(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-phenyl)-methanone

Product 1

HCID 672285532-cyclobutyl-1-(4-methylsulfanyl-phenyl)-1-(1H-pyrrolo[2,3-b]pyridin-2-yl)-ethanolYield 18.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of (1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-phenyl)-methanone (0.6 g, 1.47 mmol) in anhydrous tetrahydrofuran (5 mL) at 0° C. was added a solution of freshly prepared Grignard reagent [To a suspension of magnesium turnings (0.14 g, 5.88 mmol) in anhydrous tetrahydrofuran (5 mL) was added (bromomethyl)cyclobutane (0.44 g, 2.94 mmol) at room temperature. After initiation by iodine, the resulting solution was refluxed for 30 min, and then cooled to room temperature] dropwise. After stirring for 3 h at 0° C., the mixture was poured into brine (10 mL), extracted with ethyl acetate (3×20 mL), dried over anhydrous sodium sulfate and then concentrated in vacuo. The residue was purified by flash column chromatography (silica gel from QingDao, 200-300 mesh, 25% ethyl acetate/hexanes) afforded 2-cyclobutyl-1-(4-methylsulfanyl-phenyl)-1-(1H-pyrrolo[2,3-b]pyridin-2-yl)-ethanol (90 mg, 18%) as a white solid: LC/MS m/e calcd for C20H22N2OS [M+H]+ 339.48, observed 339.0.

Workup

  1. extractionextracted with ethyl acetate (3×20 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash column chromatography (silica gel from QingDao, 200-300 mesh, 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-79da6b0d3fb04c12b410f43bd2afbd34
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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